Antimicrobial compositions and methods of using same

ABSTRACT

Our invention pertains to various new compositions, methods for using such compositions and products treated with such compositions. Our new compositions include, among other things, certain antimicrobial agents solubilized with certain disubstituted aryl compounds.

This application is a continuation of Ser. No. 419,396, Sept. 17, 1982(now U.S. Pat. No. 4,602,011) which in turn is a continuation of Ser.No. 175,073 Aug. 4, 1980 (now abandoned) which in turn is acontinuation-in-part of Ser. No. 2,555 Jan. 11, 1979 (now abandoned)which in turn is a continuation of Ser. No. 842,933 Oct. 17, 1977 (nowabandoned) which in turn is a continuation-in-part of Ser. No. 625,741Oct. 24, 1975 (now abandoned) which in turn is a continuation-in-part ofSer. No. 364,018 May 25, 1973 (now abandoned). The benefits of 35 USC120 are claimed relative to all of these prior applications.

SECTION I

One embodiment of our invention pertains to an antimicrobial agentsolubilized with a disubstituted aryl compound having a hydrophilic andan oleophilic substituent. In one preferred embodiment the antimicrobialagent is an organometal compound, such as a metal complex of 8-hydroxyquinolinol (oxine), and the disubstituted aryl compound is an alkylbenzene sulfonic acid.

This invention relates to antimicrobial compositions and placesparticular emphasis on antimicrobial compositions that have low toxicityto plant and animal life. The increasing pressures of government and theawakening concern of the public to environmental protection are greatlyrestricting the use of time-honored antimicrobials for toxicologicalreasons. For example, in the case of fungicides which have been widelyused in the outdoor environments of agriculture and lumber treatment,many of the known effective fungicides are based upon compounds of toxicmetals, such as mercury and lead, and organic compounds such aschlorinated phenols. With increasing population growth, the demands formore and more food production and the increased need for wood and itspreservation have caused these classic fungicides to be overworked tothe extent that observable adverse effects upon man's environment havebeen felt.

Vast demands exist for compounds to control microorganisms in fieldsother than agriculture and wood preservation. These include thetreatment of fabrics to prevent mildew and rot; to inhibit and killbacterial growth; the treatment of surfaces and substrates to obtainantiseptic conditions for medical, industrial, food processing andhousehold purposes; the formulation of ink and paints to prevent moldgrowth and bacterial decomposition; the prevention and treatment ofhuman and animal diseases; and on through an almost infinite spectrum ofapplications touching our daily lives.

The disruption of the life cycle of microcellular structures hasreceived considerable study and, while there are still many unprovedtheories as to their mechanism, a number of generalities may be made.For example, it has been suggested that in probably a majority ofinstances, the toxic effect of an antimicrobial agent depends upon itsgaining access to the interior of the cell. In somewhat lesserinstances, the antimicrobial may be an effective agent through thefunctions it performs outside the cell. In this latter regard, such asin the case of fungi that excrete enzymes to metabolize cellulosicmaterials around them and absorb the digested materials, it has beenproposed that some fungi may be "starved" by chemically disrupting orsequestering the excreted enzymes.

With respect to those antimicrobials that penetrate the semipermeablemembranes of the cell, little is known of the nature of their activityonce inside the cell. Some researchers believe that they may chelatetrace amounts of metals that are necessary to support the life of themicroorganism, others have suggested that they bring with them smallamounts of metals, such as mercury, silver and copper, that are toxic tothe organism, others have suggested that some antimicrobials may oxidizefatty acids and proteins within the cell, and, in the absence of anypositive proof of the precise activity within the cell, one expert hassuggested that when an effective antimicrobial agent enters the highlycomplex and delicately balanced chemical system or the microbe, theresult is massive disruption of the system, not unlike throwing severalcats over a clothesline while their tails are tied together.

In those instances in which the antimicrobial must pass through the walland enter the microorganism cell to be effective, it was believed tofollow that, since practically all microorganisms live in an aqueousenvironment, it should be a criterion that these antimicrobials behydrophilic. While this supposition was correct with respect topenetration of the outermost layers of the microorganisms, it was laterrecognized that hydrophilic materials would be repulsed by the lipoidlayers of the cell. It was then theorized that an oleophilicantimicrobial agent should be selected, but, of course, this was notalways effective since the oleophilic (hydrophobic) agent could nottraverse the outer aqueous barrier of the cellular structure. It is nowrecognized that this dilemma may be solved by structuring a compositecompound in which one portion of it is hydrophilic and another portionof it is oleophilic.

It has also been recognized for a number of years that an oleophilicmaterial, in order to penetrate the walls of a microorganism, must havesome degree of steric compatibility with the structure of the cell wall.At least one respected writer, James G. Horsfall, in Principals ofFungicidal Action (Chronica Botanica Co. 1956, Library of Congress No.56-8265), likens the nature of an effective oleophilic group to a shapedcharge such as may be used in armor-piercing explosive shells. Horsfallsuggests that the oleophilic or fat-soluble groups should more or lessmatch the shape of the fatty groups in the cell's semipermeable membraneas, by so "shaping the charge," it will permit permeation through thecritical fatty barrier of the cell. This may be taken to mean, first ofall, that the fat-soluble group must have a length that is significantwith respect to the thickness of the cell wall. Next, the oleophilicgroup should not be unduly branched nor contain substituents so large soas to cause steric hindrance to the penetration of the "shaped charge"into and through the cell wall. A simple illustration of an oleophilic"shaped charge" is a straight-chained hydrocarbon having at least aboutsix carbon atoms in the chain.

A classic example of the use of a "shaped charge" to penetrate asemipermeable membrane of a microcell lies in the discovery ofhexylresorcinol. Here the inventor found that the germicidal propertiesof resorcinol, which were known to be only mediocre, could besignificantly improved by substituting a straight-chained six-carbonalkyl group on the benzene ring of a resorcinol molecule. The effect wasdramatic, at least from the viewpoint of commercial success, ashexylresorcinol a generation or so ago became a household word and was adisinfectant that could be found in many a home medicine cabinet.

To summarize, the prior art recognizes that it is often necessary for aneffective antimicrobial agent to pass through the semipermeable membraneof a microcell if it is to be effective in disrupting the microcellularlife. It is also known that penetration of the cell may be enhanced bythe use of certain oleophilic "shaped charges" that have stereochemicalcompatibility with the structure of the lipoid layer of the cellmembrane. It is further known that the ability of the oleophilic "shapedcharge" to penetrate a cell wall will be increased if the oleophilicgroup is associated with a hydrophilic group that will serve as itspassport through the outer aqueous barrier layer of the cell. It hasalso been recognized that many surfactants, due to their combinedhydrophilic and oleophilic properties, are sometimes effective asantimicrobials to varying degrees and in certain environments.

An objective of our invention is to provide an antimicrobial compositionthat is effective in controlling a wide spectrum of microorganisms andwhich has relatively low toxicity toward animal and plant life. Theseand other objects of this invention are accomplished by formulating asolution comprised of an active antimicrobial agent and a disubstitutedaryl compound in which the first substituent is an oleophilic groupadapted to penetrate the lipoid layers of microcells and the secondsubstitutent is a hydrophilic group. While it is believed necessary toform an initial solution of the antimicrobial agent with thedisubstituted aryl compound, the antimicrobial agent may, when dilutedfor use, begin to precipitate from solution. This precipitation fromsolution may and usually will become complete after the composition hasbeen applied to a substrate.

DETAILED DESCRIPTION The Oleophilic Substituent

The oleophilic substituent of the composition of this invention shouldhave a degree of stereochemical compatibility with the structure of thesemipermeable membrane of the cell of a microorganism. As recognized inthe prior art, a common structure meeting this criterion is anessentially unsubstituted straight-chained hydrocarbon having a lengththat is significant with respect to the thickness of a cell wall. Thisgenerally requires, as a minimum, an alkyl chain with about six carbonatoms in it. The alkyl chain, on the other hand, should not be too longsince the mobility of an alkyl chain increases with increasing chainlength and alkyl chains will begin to coil if they are too long. Whenthe coiling becomes significant, it can cause steric hindrance and makepermeation of the cell wall difficult. While the maximum length of thealkyl chain can only be determined with respect to a given environmentand a specific cell structure, it is believed to be a fairgeneralization to suggest that an alkyl chain much longer than 18 carbonatoms and, more especially, one longer than 24 carbon atoms, will loseits effectiveness in penetrating the cell wall.

The preferred alkyl groups of this invention are not excessivelybranched or substituted in the sense that they will result in sterichindrance. Nonetheless, some substitutes along the hydrocarbon chain,such as chlorine, may improve the oleophilic properties of the "shapedcharge" and may be used to advantage. It has been observed thatjudicious chlorine substitution may permit the use of shorter alkylchains.

Throughout the specification and examples, the alkyl aryl sulfonic acidsare referred to in language that might suggest pure substances. Forinstance, dodecyl benzene sulfonic acid (DDBSA) is benzene sulfonic acidwith a 12-carbon alkyl chain attached to the benzene ring, but the DDBSAactually employed in the examples is a typical sulfonic acidcommercially available comprised of a complex alkyl benzene which is areaction product of benzene with the tetramer of propylene. Such alkylbenzenes are mixtures wherein the average alkyl chain length determinesthe name given to the product. This so-called DDBSA, with a typical M.W.of 237 as specified by one manufacturer, may contain side chain lengths,from about C₂ to C₂₀, more than one side chain, and side chains invarying positions on the aryl ring. A usual specification for DDBSA willcall for a minimum of 85% C₁₀ through C₁₂ alkyl side chain lengths.

Similarly, while C₆ to C₂₄ side chain lengths are claimed in thisinvention, this actually refers to the approximate average length, suchaverages being obtainable by use of alkyl aryl sulfo compounds asreceived from a producer, or by mixtures of two or more compounds, eachwith a different average alkyl side chain length.

Pure long-side-chain alkyl aryl sulfonic acids will function in thisinvention, but have no practical value because they are not availablecommercially and because of the extremely high cost.

To determine differences in antifungal efficacy and physicalcharacteristics of compositions of the invention prepared with Cu-8-Qand a range of alkyl aryl sulfonic acids, carbon chain lengths of thealkyl group attached to the aryl group varying from C₈ to C₁₅ weretested. These included C₈ (octyl benzene sulfonic acid), C₁₀ (decylbenzene sulfonic acid), C₁₂ (dodecyl benzene sulfonic acid--DDBSA), C₁₃(tridecyl benzene sulfonic acid) and C₁₅ (pentadecyl benzene sulfonicacid). Determination of antifungal efficiency was made by the testmethod of Example 1 set forth below.

It was determined that optimum antifungal efficacy was obtained in theC₁₀ to C₁₃ range, with C₁₂ (DDBSA) being the best, by a small margin oflittle practical consequence for most applications, all-aroundsolubilization of antimicrobial agents such as metal complexes of oxine.A small but significant reduction in efficacy resulted from the use ofC₈ and C₁₅, although use of both are within the scope of this invention.

It also was determined that optimum handlingcharacteristics--concentrate and use-dilutions stability, ease ofdilution with water, low temperature concentrate viscosity, maximumamount of antimicrobial agents incorporatable in the concentrate,etc.--of compositions of the invention were obtained generally with C₁₂,although differences with C₁₀ and C₁₃ were small to insignificant inmost use instances.

C₁₅, because of its greater lipophilic character, exhibits diminishedwater solubility, a matter of practical consequence since water is thepreferred use diluent for most end uses of the compositions of thisinvention. The increased lipophilic character imported to thecompositions by the C₁₅ alkyl chain exerted no adverse effect upongeneral organic solvent solubility of the invention compositions and isof benefit in those end uses where, for a variety of reasons, anon-water carrier is desired.

Lastly, it is within the scope of the invention to employ mixtures ofsulfonic acids including alkyl side chains of C₀ and C₁ with C₈ to C₂₄.

No rigid definition can be given as to the length, composition andconfiguration of the oleophilic group and these parameters necessarilymust be adjusted for the microbial genus and species that are to becontrolled. It is believed, however, that given the insight provided bythis specification, it will be within the skill of a worker of ordinaryskill in the art to select, with minimum effort, an oleophilicsubstituent that will permeate the lipoid layer of a microcellularorganism in the practice of this invention.

The Hydrophilic Substituent

The hydrophilic substituent of the aryl compound should be ionizable andcontribute to the solubilization of the antimicrobial agent. Two of themost effective and chemically accessable such substituents that willaccomplish this purpose are the sulfo and the hydroxyl radicals.

The Aryl Compound

A preferred aryl compound is benzene which is believed to be mosteffective and, perhaps to a lesser extent, naphthalene. Aryl compoundscomprised of more than two ring structures may lose their effectivenessfor several reasons, among them being the fact that their size becomeslarge as compared with the oleophilic substituent and will tendsterically to hinder the oleophilic substituent in penetrating the wallof the microorganism. While not essential in the practice of thisinvention, tertiary substituents of the aryl group may sometimes provedesirable, particularly if they are capable of withdrawing electrons toimprove the solubilization of the antimicrobial agent. Substituentswhich may function in this manner are, for example, --NO₂, --CN and--CHO. Electron-withdrawing substituents should be used sparingly andwith discretion to avoid overloading of the ring structure of the arylcompound.

The Antimicrobial Agent

As set forth above, the antimicrobial agent must be able to form asolution with the substituted aryl compound, at least in the initialformation of a concentrate which may later be diluted prior to use.

One particular advantage of this invention lies in the fact thatantimicrobial agents that have known low toxicity toward plant andanimal life may be made more effective by solubilizing them inaccordance with this invention, thus greatly increasing their utility.Of these, for example, the metal complexes (chelates) of 8-hydroxyquinolinol (oxine), and especially copper-8-quinolinolate (Cu-8-Q), arequite prominent due to their comparatively low toxicity toward human,animal and plant life.

Another unexpected result that accrues through the practice of thisinvention lies in the fact that when an aryl-alkyl sulfonic acid issolubilized with a metal-8-Q, the solution is far less irritating tobody tissue and skin than is the aryl-alkyl sulfonic acid by itself. Forexample, in tolerance tests conducted on sensitive areas of the humanskin, solutions of DDBSA and Cu-8-Q diluted 1:200 with water were notonly found to be less irritating than DDBSA at the same dilution, butalso less irritating than cleansing agents generally accepted as being"mild" such as Ivory soap.

It has been discovered that not only are antimicrobial agents such asmetal complexes of oxine readily soluble in the substituted arylcompounds of this invention, but also their effectiveness as anantimicrobial is materially increased over formulations of theseantimicrobial agents known to the prior art. As will be demonstrated inthe following examples, when Cu-8-Q, for example, is solubilized bydodecyl benzene sulfonic acid (a substituted aryl compound of thisinvention), its effectiveness in controlling the growth ofmicroorganisms improves dramatically.

In addition to Cu-8-Q, other metal complexes of oxine are known to beeffective antimicrobials. Of these, mercury is generally regarded asbeing more effective than copper, and the following is a listing takenfrom literature references of the relative effectiveness of severalmetal quinolinolates in descending order of activity: mercury, copper,cadmium, nickel, lead, cobalt, zinc, iron and calcium. Aluminum and tinare also useful.

Antimicrobials other than metal oxines may be solubilized in thealkyl-aryl sulfonic acids of the invention, both alone and in thepresence of the metal oxines. For a variety of specialized requirements,such other antimicrobials have significant utility, not only forantimicrobial properties, but also because of the considerable handlingand application advantages of true solution formulations in thoseinstances where the antimicrobial normally is not water-soluble and mustbe applied either as a dust or as a particulate suspension in water.Among the antimicrobials which are useful are these classes:

1. Oxine and derivatives thereof.

2. Chlorophenols such as tri-, tetra- and penta-chlorophenol.

3. Anilides such as 2,5-dimethyl-3-furylanilide.

4. Benzimidazoles such as 2-(methoxy-carbamoyl)benzimidazole.

5. Nitrophenols such as dinitrophenol.

6. Nitrocresols such as dinitrocresol.

7. Crotonates such as 2,4-dinitro-6-(2-octyl)phenyl crotonate.

8. Organotins such as triphenyltin acetate and tributyl tinoxide.

9. Antibiotics such as streptomycin and griseofulvin.

10. Organic acids such as acetic, sorbic, salicylic, benzoic,dehydroacetic and undecylenic acids.

11. Oxathiius such as 5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide.

12. Sulfones such as diiodomethyl-p-tolyl sulfone.

13. Iodine, compounds thereof, and iodofors.

14. Aliphatic alcohols from C₁ to C₁₈ chain length.

15. Alkyl, benzyl and phenyl alcohols.

16. Hydroxyl diphenyl oxide and sulfide isomers.

17. Carbanilides such as trichlorocarbanilide.

18. Bis phenols such as hexachlorophene.

19. Phenyl mercurials such as phenyl mercuric acetate and nitrate.

20. Complex organic mercurials such as thimersol and nitromersol.

21. Aldehydes such as formaldehyde and glutaraldehyde.

22. Aniline derivatives such as 2,6-dichloro-4-nitroaniline.

23. Diphenyl ethers such as 2,4,4'-trichloro-2'-hydroxyl diphenyl ether.

24. Miscellaneous types including silver oxine; chlorhexidine andwater-soluble acetate and gluconate derivatives thereof; imidazolidinylurea; hexylresorcinol;3(2-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroethyl)glutarimide;benzoaminobenzene sulfonate; 3,ethylidene-L-azetidine-2-carboxylic acid;4,6-dichloro-N-(2-chlorophenyl)-1,3,5-triazin-2-amine;N,N'-(piperazinediyl bis(2,2,2-trichloroethylidene) bis(formamide);salicyanilide-2-hydroxy-N-phenylbenzimide; hexachlorobenzene; boricacid; 5,6,7,8-tetrachloroquinoxaline; 1-hydroxypyridine;2-n-octyl-4-isothiazolin-3-one; 1,2-benzisothiazolin-3-one;p-chlorophenyl-3-iodopropargyl formol; dimethyloldimethylhydantoin-1,3-bis(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidine-dione;7-(cis-3-chloro-2-propenyl-1,3,5-triazo-7-azoniatricyclo[3.3.1.1.³,7]decane.

In the examples that follow, two methods were used for incorporating ametal-oxine complex into the composition of the invention: (a) theaddition of the complex itself, and (b) the in situ formation of thecomplex in the compositions. The latter often is preferable for economicand versatility reasons.

For in situ formation, an appropriate metal compound is used forreaction with oxine. In the case of Cu-8-Q, for example, copper hydrate,copper sulfate, copper acetate, copper chloride and copper naphthenateare among the suitable sources of copper. The actual choice depends onthe economics (some copper compounds are cheaper copper sources thanothers), nature of by-product (copper hydrate and oxine form water;copper acetate plus oxine form acetic acid, etc.); ease of reaction(some copper compounds release copper to form the copper-oxine chelateeasily; others do so more slowly and only under more severe reactionconditions). All are within the scope of this invention. This is truealso of in situ formation of metal-oxine chelates other than copper.

Generally, oxine itself is the preferred raw material for preparation ofthe metal chelate inasmuch as oxine itself is effective, more readilyavailable and lower in cost than substituted chelating oxines. Thelatter, however, are within the scope of this invention and have utilityin certain medical applications where more costly substituted oxines isnot such a significant limitation.

Generally, the full metal chelate of oxine is the preferred form, buttwo variants of full chelates are within the scope of this invention:(a) half-chelates in the case of metals with a valency of two or more,such as copper, and (b) a stoichiometric excess or deficiency of metalrequired to produce the full chelate.

A polar diluent is used with the mixture of DDBSA and Cu-8-Q which notonly serves as a viscosity-reducing agent, but also permits ionizationof the alkyl benzene sulfonic acid to achieve complete solubility of theCu-8-Q. It has been found that complete solubilization is effectedthrough the use of a highly polar organic solvent which, for purposes ofeconomy in diluting the solution for end use applications, is preferablywater-miscible. A partial list of suitable diluents for use in thepresent invention is given below:

Methanol

Ethanol

Isopropanol

n-Butanol

Dimethylformamide

N-methyl-2-pyrrolidone

Ethylene glycol

Propylene glycol

Water

Broadly speaking, for every part by weight of the metal-8-quinolinolate,it is preferred to include from 5 to 50 parts by weight DDBSA and 1 to50 parts by weight of the polar diluent. The most preferred compositionaccording to the present invention contains from 2 to 10 parts by weightof Cu-8-Q, 25 to 83 parts by weight of the alkyl benzene sulfonic acid,and 15 to 35 parts by weight of the diluent per 100 parts by weight ofthe concentrate. One specific composition produced according to thepresent invention contains about 5 parts by weight of Cu-8-Q, about 64parts by weight of DDBSA, and about 31 parts by weight of methanol.Additionally, it has been found useful to add minor amounts, e.g., 5% byweight, of ethylene glycol to improve shelf life.

The concentrates prepared as above are diluted with a carrier,preferably water, prior to use, and essentially may be diluted to anydegree. Other carriers may be used, including xylene, isopropanol,ethylene glycol and naphtha. The diluted solutions can be applied by aknown technique, such as brushing, spraying, dipping or wiping.

EXAMPLES Examples 1-22

In the examples that follow, the effectiveness of the variousformulations was determined by treating freshly cut pine boards by dipimmersion for 10 seconds in the formulation to be tested. The boards,along with an untreated control, were placed in a chamber for the periodof time indicated and maintained at a temperature of about 80° F. and ahumidity of about 70%.

At the end of the test period, the boards were removed from the chamberand rated for effectiveness in terms of percentage of total surface areacovered by fungal stain and mold growth. Accordingly, the lower thepercentage, the higher the effectiveness of the test formulation.

Unless otherwise indicated, the tabularized formulations wereconcentrates that were diluted with a carrier, as indicated, prior toapplication to the substrate. All parts given in these and otherexamples are parts by weight, unless otherwise noted.

    ______________________________________                                        Ex-                                  % Fungal                                 am-  Cu-8-Q   Solubilizing Diluent   Growth                                   ple  Amount   Agent (amount                                                                              (amount)  (42 days)                                ______________________________________                                        1    10       DDBSA (50)   Methanol (40)                                                                           29                                       2    10       98% H.sub.2 SO.sub.4 (20)                                                                  Water (70)                                                                              53                                       3    10       Maleic acid (50)                                                                           Water (40)                                                                              58                                       4    Untreated control boards  74-90                                          5    5        DDBSA (64)   Methanol (31)                                                                           17                                       6    5        p-toluene sulfonic                                                                         Methanol (31)                                                                           52                                                     acid (64)                                                       7    5        1-naphthalene sul-                                                                         Methanol (31)                                                                           74                                                     fonic acid (64)                                                 8    5        Benzene sulfonic                                                                           Methanol (31)                                                                           92                                                     acid (64)                                                       9    5        Methane sulfonic                                                                           Methanol (31)                                                                           62                                                     acid (64)                                                       10   Untreated control boards  90                                             ______________________________________                                         (Use dilution in above examples 400:1 with water carrier.)               

In each of the above examples, the Cu-8-Q formed a true solution withthe solubilizing agent, both as a concentrate and when diluted for usewith the water carrier. These examples show that solubilization of theantimicrobial agent is not sufficient to obtain the desired results ofthis invention, but that the solubilizing agent must be selected inaccordance with the criteria discussed above, such as is the case withDDBSA which is a disubstituted aryl compound having the definedoleophilic and hydrophilic substituents.

In the following examples, the very real improved antifungal activityachieved in the practice of this invention is demonstrated. Cu-8-Q andDDBSA were tested separately and combined to determine efficacy incontrol of sapstain and mold on fresh cut green lumber. Also compared isNylate 10 (Seymour Chemical Company), a commercially available,solubilized Cu-8-Q and water emulsifiable concentrate (10% Cu-8-Q). Foruse, Nylate 10 was diluted 1:200 with water.

    ______________________________________                                        Ex-                                                                           am-                        % Fungal Growth                                    ple  Composition           (28 days)                                          ______________________________________                                        11   Nylate 10 aqueous emulsion, 0.05%                                                                   72                                                      Cu-8-Q                                                                   12   0.025% Cu-8-Q aqueous suspension                                                                    89                                                      (prepared by ball milling)                                               13   0.35% DDBSA aqueous solution                                                                        49                                                 14   Prepared by mixing the composition                                                                   6                                                      of Examples 12 and 13 to form a solu-                                         tion comprised of 0.025% Cu-8-Q and                                           0.35% DDBSA                                                              ______________________________________                                    

The performance of the composition of the invention (Example 14) is muchsuperior to that of Cu-8-Q or DDBSA alone and to that of a conventionalsolubilized Cu-8-Q/water emulsion.

In order to demonstrate the effectiveness of this invention as anantifungal, sapstain and mold control, comparisons were made with twostandard, widely used antifungal compositions.

    ______________________________________                                                                     % Fungal                                                                      Growth                                           Ex-                          (28 days)                                        am-                          Test   Test                                      ple  Composition             #1     #2                                        ______________________________________                                        15   Sodium tetrachlorophenate                                                                        16.40%   20   7                                            Other sodium chlorophenates                                                                      4.43%                                                      Phenyl mercuric lactate                                                                          0.40%                                                      Inerts             78.77%                                                     (Use dilution - 1:100 in water)                                          16   Sodium pentachlorophenate                                                                        31.6%    20   0                                            Other sodium chlorophenols                                                                       4.4%                                                       Borax (sodium tetraborate                                                                        57.0%                                                      10 H.sub.2 O)                                                                 Inerts             7.0%                                                       (Use dilution - 10 pounds per                                                 100 gallons of water)                                                    17   Cu-8-Q             10.0%    17   0                                            DDBSA              50.0%                                                      Methanol           40.0%                                                 (Use dilution - 1:200 in water carrier)                                       ______________________________________                                    

To demonstrate the antifungal properties of various metal-oxinechelates, compositions were prepared using 6 parts by weight of theindicated meta-oxine plus 64 parts DDBSA plus 31 parts methanol. Thesecompositions were diluted 1:200 with a water carrier for use.

    ______________________________________                                                              % Fungal Growth                                         Example    Metal-Oxine                                                                              (28 days)                                               ______________________________________                                        18         Copper     17                                                      19         Tin        20                                                      20         Aluminum   28                                                      21         Nickel     39                                                      22         Zinc       46                                                      ______________________________________                                    

The foregoing metal-oxines (metal-8-quinolinolates) also may be preparedin situ in the compositions by reacting oxine with any of a number ofappropriate metal compounds. Although the copper chelate of oxinegenerally is the most effective and versatile for a broad range of enduses, other metal-oxine chelates have utility.

Example 23

The following DDBSA/Cu-8-Q solution was prepared in accordance withpreviously stated techniques. (In this instance, Cu-8-Q was formed insitu from copper hydrate and oxine, also known as 8-hydroxy quinoline.)

Copper hydrate 1.70

Oxine 4.44

DDBSA 64.81

Methanol 15.05

Isopropanol 14.00

This composition was diluted with a water carrier, as tabularized below,and tested in comparison with a sodium tetrachlorophenate (23%) liquidconcentrate, also diluted in a water carrier, against organisms on threespecies of green lumber--Douglas fir, Amabilis fir and Ponderosa pine.The organisms were:

Cephaloascus fragans a brown mold that infects certain wood species

Trichoderma virgatum a common mold

Mixed spores a combination of two molds (Penicillium sp. and Aspergillisniger) and a fungus (Ceratocystis pilifera that causes blue stain inwood.

The freshly cut wood samples were dip treated (15-second immersion) withthe test fungicides and then innoculated with spore suspensions of theabove-described fungi. The test boards plus untreated control boardswere then placed in a warm, humid chamber for four weeks. The resultsare set forth in the table below in which:

    ______________________________________                                        A = Douglas fir 0 = no growth                                                 B = Amabilis fir                                                                              1 = no growth for 2 weeks                                     C = Ponderosa pine                                                                            2 = medium growth                                                             3 = heavy growth in 4 weeks                                                   4 = heavy growth in 2 weeks                                   ______________________________________                                                 Use   C.        T.        Mixed                                               Dilu- fragans   virgatum  spores                                                tion    A     B   C   A   B   C   A   B   C                        ______________________________________                                        Tetrachloro-                                                                             1:100   4     4   4   0   0   3   3   4   4                        phenol                                                                        composition                                                                   DDBSA/Cu-8-Q                                                                             1:240   2     0   1   3   0   4   4   3   4                        solution                                                                      Tetrachloro-                                                                             1:50    2     0   4   0   0   1   3   2   4                        phenol                                                                        composition                                                                   DDBSA/Cu-8-Q                                                                             1:120   0     0   1   3   0   1   2   2   2                        solution                                                                      Tetrachloro-                                                                             1:25    2     2   3   0   0   1   0   0   3                        phenol                                                                        composition                                                                   DDBSA/Cu-8-Q                                                                             1:60    0     0   0   1   0   0   0   0   0                        solution                                                                      Tetrachloro-                                                                             1:12.5  0     1   0   0   0   0   0   0   2                        phenol                                                                        composition                                                                   DDBSA/Cu-8-Q                                                                             1:30    0     0   0   0   0   0   0   0   0                        solution                                                                      Control (no        4     4   4   3   4   4   4   4   4                        treatment)                                                                    ______________________________________                                    

Example 24

To further illustrate the antifungal properties of compositions of theinvention, the formulation below was prepared and tested as apreservative against microbiological deterioration of 10 oz. cotton duckcloth and compared with untreated cotton duck as a control and withCunilate 2174, a commercially available concentrate containing 10%Cu-8-Q which is made soluble in petroleum hydrocarbon solvents via useof nickel acetate and 2-ethyl hexoic acid. The previously describedNylate 10 also was tested.

Oxine 4.1 parts by weight

Copper hydrate 1.4 parts by weight

DDBSA 64.0 parts by weight

Propylene glycol methyl ether 30.5 parts by weight

This composition was use-diluted 1:24 with a water carrier; the Cunilate2174 was diluted 1:19 and 1:9 with mineral spirits for use; the Nylate10 was diluted 1:19 and 1:9 with water. The cotton samples were dippedto refusal in the test compositions, air-dried and buried at 75° F. for29 days in sheep manure moistened with water. Microorganism attack onthe cotton cloth in this test medium is both rapid and severe as can benoted from the essentially total destruction of the untreated controlcloth sample. The results of this test are tabulated as follows:

    ______________________________________                                                       Weight of Cu-8-Q                                                                           Estimated                                         Composition (dilution)                                                                       in Cloth     Strength Loss*                                    ______________________________________                                        Untreated control                                                                            0            100%                                              Cunilate 2174 (1:19)                                                                         0.41 gram    50%                                               Cunilate 2174 (1:9)                                                                          0.84 gram    25%                                               Nylate 10 (1:19)                                                                             0.61 gram    50%                                               Nylate 10 (1:9)                                                                              1.21 gram     0%                                               DDBSA/Cu-8-Q (1:24)                                                                          0.18 gram     0%                                               ______________________________________                                         *As measured by tear strength reduction:                                      100% = total loss of strength                                                 50% = moderately difficult to tear by hand                                    25% = difficult to tear by hand                                               0% = impossible to tear by hand                                          

The superiority of the formulation of the invention over other Cu-8-Qcompositions is clearly evident.

Example 25

The following composition was tested for minimum fungicidalconcentration and compared to two well known antifungalchemicals--pentachlorophenol and 2,3,5 trichloro-4-propyl-sulfonylpyridine--and DDBSA.

Oxine 8.2 parts by weight

Copper hydrate 2.8 parts by weight

DDBSA 59.0 parts by weight

Propylene glycol methyl ether 30.0 parts by weight

All of the test composition concentrations to be tested wereincorporated in the fungal growth media (agar) in accordance withstandard microbiological practices. Agar plugs containing the testfungicides then were inoculated with a sporulating culture andinoculated at the temperatures and times specified by The American TypeCulture Collection (ATCC) recommendations. The plugs were then scoredfor absence or presence of organism growth. The results are shown in thefollowing table. Minimum fungicidal concentrations were determinedagainst a broad spectrum of fungi that are detrimental to man,foodstuffs and materials and which can result in metabolite formations(mycotoxins) of extreme toxicity to man and animals.

In the table below, Composition A is that of this Example 25 and theactive ingredient is Cu-8-Q;0; Composition B is DDBSA; Composition C ispentachlorophenol; and Composition D is 2,3,5-trichloro-4-propylsulfonylpyridine. Where no concentration is listed, no data is available. Thestated value of "1" means 1 or fewer ppm.

    ______________________________________                                                     Minimum Fungicidal Concentration                                              (ppm of active ingredient)                                                    A     B         C        D                                       ______________________________________                                        Aspergillis niger                                                                            1       10,000    1-3    --                                    (ATCC 9642)                                                                   Aspergillis terreus                                                                          1       100       --     36                                    (ATCC 10609)                                                                  Aspergillis flavus                                                                           1       1,000     22-54  --                                    (ATCC 11655)                                                                  Alternaria alternata                                                                         1       --        --     --                                    (ATCC 13963)                                                                  Aureobasidium pullulans                                                                      1       100       --     --                                    (ATCC 16624)                                                                  Lenzites trabea                                                                              1       100       1-3    --                                    (ATCC 11539)                                                                  Polyporus tulipiferae                                                                        1       100       1-3    --                                    (ATCC 11245)                                                                  Penicillium brevi                                                                            1       100       --     --                                    compactum (ATCC 16024)                                                        Rhizopus stolonifer                                                                          1       100       1-3    --                                    (ATCC 24794)                                                                  Trichoderma viride                                                                           10      100       --     --                                    (ATCC 8678)                                                                   Trichoderma sp.                                                                              1       100       --     --                                    (ATCC 12668)                                                                  Candida albicans                                                                             1       1,000     --      3                                    (ATCC 10259)                                                                  ______________________________________                                    

These results illustrate the high efficacy of the composition of thisinvention and confirm the fact that an antifungal composition preparedfrom a Cu-8-Q/DDBSA solution is much superior to DDBSA alone. Theresults also indicate the favorable relative efficacy of the testcomposition compared to the two commercially available fungicides ofrecognized high performance.

Example 26

Test compositions were evaluated as wood preservatives via a standardsoil block culture procedure (ASTM D4131-61) wherein the wood blockswere water-leached in accordance with standard technique prior toexposure to the test fungus. The test fungi were those specified forwood decay evaluation by the American Wood Preservers' Association(AWPA)--namely, Lenzites trabea (Madison 617, ATCC 11539) which is thestandard test fungus for above-ground wood exposure, and Poria monticola(Madison 698, ATCC 11538) which is the standard copper-tolerant fungusfor ground contact wood use.

In the table below, the results are expressed as percentage weight lossof the wood test blocks from decay fungi attack.

Composition A is comprised of:

Oxine 4.42 parts by weight

Copper hydrate 1.51 parts by weight

DDBSA 64.07 parts by weight

Methanol 30.00 parts by weight

The composition was diluted 1:110 in a water carrier for impregnation ofthe L. trabea test blocks and 1:55 for test against P. monticola.

Composition B was the same as Composition A except that it was diluted1:55 with toluene carrier for block impregnation for test against bothtest fungi.

Composition C was the same as the DDBSA/Cu-8-Q solution of Example 25diluted with a water carrier 1:220 for test against L. trabea and 1:55against P. monticola.

Cunilate 2174 was diluted 1:110 with a toluene carrier.

The abbreviation "pcf" means pounds of Cu-8-Q per cubic foot of wood.

    ______________________________________                                                 Lenzites trabea                                                                             Poria monticola                                                   Retention Weight    Retention                                                                            Weight                                  Composition                                                                              (pcf)     Loss (%)  (pcf)  Loss (%)                                ______________________________________                                        A          0.021     0.3       0.040  1.3                                     B          0.025     5.0       0.029  11.3                                    C          0.018     2.0       0.036  8.1                                     Cunilate 2174                                                                            0.024     13.6      0.026  43.4                                    Untreated control                                                                        0         45.3      0      55.1                                    ______________________________________                                    

These results demonstrate the efficacy of the compositions of theinvention in both a water and an organic solvent (toluene) carrier. Alsoillustrated is the greatly improved efficacy over Cunilate 2174,especially for wood in ground contact service. The wood protectionresults with Compositions A, B and C compare favorably with those ofpentachlorophenol (PCP), tested simultaneously, wherein PCP, a worldstandard for wood preservation, exhibited 1.4% weight loss at 0.30 pcfretention against L. trabea and 3.1% weight loss at 0.27 pcf retentionin the wood against P. moniticola.

Employing AWPA Test Method M12-72 (revised 1973) for testing wood blockresistance to termite (Reticulitermes flavipes) attack, it wasdetermined that no attack occurred at retentions of Composition Aadequate to protect the wood from decay.

Example 27

The purpose of this test was to determine antifungal efficacy ofDDBSA/Cu-8-Q solutions and to compare their efficacy to that of a worldstandard, sodium pentachlorophenate, and a mixture of two well-knownagricultural fungicides, Topsin M (a thiophenate) and Nabam (athiocarbomate). The test method is designated as a proposal for theFinnish NWPC Standard No. 1.4.1.3/1974. The test substrate was freshcut, green pine wood. The test fungi were:

Blue stain fungi--mixture of Ceratocystis pilifera ZII Sclerophomaentoxylina Z17 Pullularia pullulans U2

Mold fungi--mixture of Paecilomyces varioti X15 Cladosporiumsphaerospermum R7 Aspergillis amstelodami X19

In the table below, Composition A is the formulation of Example 5diluted 1:200 with a water carrier.

Composition B is the formulation of Example 5 diluted 1:100 with a watercarrier.

Composition C is a 1.5% concentration of sodium pentachlorophenate inwater.

Composition D is a 0.4% concentration in water of a 47:53 weight ratioof Topsin M:Nabam.

E refers to untreated control pine boards.

The rating index is:

0=no visible growth

1=traces of growth

2=slight growth

3=moderate growth

4=covered with fungi

    ______________________________________                                                      Test Composition                                                              A     B     C       D   E                                       ______________________________________                                        Blue stain fungi growth                                                                       0.8     0.3   0.5   2.5 3.9                                   Mold fungi growth                                                                             0.5     0     0.3   1.3 3.6                                   ______________________________________                                    

The demonstrated efficacy of Compositions A and B against the six listedfungal organisms has utility not only on the tested substrate--wood--butalso for protection of a variety of other materials that are attacked byone or more of the fungi, including paint, concrete, brick, textiles andleather.

Example 28

Using the standard AOAC fungicidal test method (12th Edition, 1975), thecomposition below was evaluated against two widespread fungi.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Isopropanol 32.00 parts by weight

Demineralized water 25.22 parts by weight

The two fungi were Aspergillis niger, a ubiquitous black fungus whichflourishes on a broad range of substrates, and Trichophytonmentagrophytes, a cause of "athlete's foot."

A. niger--at 1:200 use dilution in a water carrier, no growth after 10minutes' exposure.

T. mentagrophytes--at 1:750 use dilution in a water carrier, no growthafter 10 minutes' exposure.

Similar but somewhat lower efficacy results were obtained bysubstituting zinc-8-Q or aluminum-8-Q in the composition of thisexample, produced by reacting zinc oxide and aluminum hydroxiderespectively with oxine.

Example 29

The compositions of this invention exhibit efficacy against a broadspectrum fungal plant pathogens, as illustrated by various use dilutionsin a water carrier of the following composition:

Copper hydrate 1.70 parts by weight

8-hydroxy quinoline 4.44 parts by weight

Isopropanol 35.00 parts by weight

DDBSA 58.86 parts by weight

A. Valencia Oranges

Tested on harvested fruit against Phomopsis stemend rot and Diplodisrot, at a 1:100 use dilution, 2-minute dip application. After 3 weeks at70° F., the following percentages of decay were noted:

Control (untreated) oranges--9.5% decay

Treated oranges--5.3% decay

B. Sugar Cane

An agar seeding test against Ceratocystis paradoxa (pineapple disease)at a 1:10,000 (100 ppm) use dilution yielded a 3.0 mm. inhibition zone.

C. Peach Trees

Tested against Taphrina deformans (causes leaf curl disease). Four testtrees were sprayed twice, two weeks apart, with a 1:400 use dilution.Three months later, 100 leaves on each test tree were rated for leafcurl:

Control (untreated) leaves--100% leaf curl

Treated leaves--13.5% leaf curl

D. Cotton

Effectiveness against 11 fungi and 1 bacterium (Xanthomonas malvacearum)that are associated with disease of cottonseed, seedlings and otherplants was evaluated in vitro, using the following compositions:

    ______________________________________                                        Composition #1                                                                           Copper hydrate                                                                              1.70    parts by weight                                         8-hydroxy quinoline                                                                         4.44    parts by weight                                         Methanol      4.00    parts by weight                                         Isopropanol   30.86   parts by weight                                         DDBSA         59.00   parts by weight                              Composition #2                                                                           Copper hydrate                                                                              2.80    parts by weight                                         8-hydroxy quinoline                                                                         8.20    parts by weight                                         Methanol      4.00    parts by weight                                         Isopropanol   26.00   parts by weight                                         DDBSA         59.00   parts by weight                              ______________________________________                                    

Both compositions were prepared in accordance with procedures stated inprevious examples.

The following results were obtained, expressed in parts per million(ppm) of total test composition in water carrier and the relative growthinhibition provided at each test strength on each tested organism. Inthe tables below:

0=no apparent inhibition

1=some inhibition

2=considerable inhibition (little growth)

3=total inhibition (no growth)

    ______________________________________                                                     Concentrations (ppm)                                             Test Organisms 0     1     5   25   100  500  1000                            ______________________________________                                        Composition #1                                                                Pythium ultimum (41B)                                                                        0     0     0   1    2    3    3                               Rhizoctonia solani (1D)                                                                      0     0     0   1    2    3    3                               Fusarium (4A)  0     0     0   3    3    3    3                               Fusarium (4D)  0     1     1   2    2    2    3                               Fusarium roseum (4C)                                                                         0     0     0   1    2    2    3                               Colletotrichum 0     0     0   1    2    2    2                               gossypii (35A)                                                                Xanthomonas    0     0     0   0    2    2    3                               malvacearum (2A)                                                              Composition #2                                                                Pythium ultimum (41B)                                                                        0     0     1   2    2    2    2                               Rhizoctonia solani (1D)                                                                      0     0     1   2    2    2    2                               Fusarium (4A)  0     0     1   1    1    2    2                               Fusarium (4D)  0     0     1   1    2    2    2                               Fusarium roseum (4C)                                                                         0     0     0   2    2    2    2                               Colletotrichum 0     0     0   2    2    2    2                               gossypii (35A)                                                                Xanthomonas    0     0     0   1    1    2    2                               malvacearum (2A)                                                              ______________________________________                                                      Concentrations (ppm)                                            Test Organisms  500      1000                                                 ______________________________________                                        Composition #1                                                                Aspergillis sp. 1        1                                                    Helminthosporium oryzae                                                                       2        2                                                    Mucor mucedo    1        1                                                    Penicillium sp. 1        1                                                    Rhizopus sp.    1        1                                                    ______________________________________                                    

Example 30

The composition of Example 28 was screened for fungal pathogen responseas a foliar spray on beans and rice. The rating scale is from 0 (nopathogen control) to 10 (complete pathogen control). The concentrationof active ingredient (in a water carrier) of all compositions tested is33 parts per million (ppm). The active ingredient in the composition ofExample 28 is expressed in terms of Cu-8-Q and the chemical as listedbelow for four comparative products. The comparative products testedwere Karathane (2,4-dinitro-6-(2-octyl phenyl crotonate), Vitavax(5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide), Daconil(tetrachloroisophthalonitrile) and Maneb (manganeseethylenebisdithiocarbamate). The plants and diseases tested were beanmildew (Erysiphe polygoni), bean rust (Uromyces phaseoli typica) andrice spot (Helminthosporium orazae and Cerocospora orazae).

    ______________________________________                                                    Bean Mildew                                                                            Bean Rust Rice Spot                                      ______________________________________                                        Example 28 composition                                                                       8         10        10                                         Karathane     10         --        --                                         Vitavax       --          9        --                                         Daconil       --         --        10                                         Maneb         --         --         8                                         ______________________________________                                    

Example 31

The following composition was evaluated (diluted with water for use) invitro for inhibition against two fungal pathogens, Botrytis sp. andAlternaria sp., causal agents of a variety of plant diseases.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

The zone of inhibition agar plate test also was used to test Cunilate2174 (diluted in mineral spirits for use) for comparison. Thecomposition concentrations in the table of results below are expressedin parts per million (ppm) of Cu-8-Q. The larger the inhibition zone,the greater is the efficacy of the composition.

    ______________________________________                                                   Botrytis    Alternaria                                             ______________________________________                                        DDBSA/Cu-8-Q                                                                  Concentration (ppm)                                                                        21     50     125   21   50   125                                Inhibition zone (mm)                                                                       13     15      22    0   16    21                                Cunilate 2174                                                                 Concentration (ppm)                                                                        83     200    500   83   200  500                                Inhibition zone (mm)                                                                       13     14      16    0    0    14                                ______________________________________                                    

The DDBSA/Cu-8-Q solution of this invention exhibits an improvement inefficacy against the tested organisms by a factor of 4x in the case ofBotrytis to 10x in the case of Alternaria.

Example 32

The DDBSA/Cu-8-Q solution of the preceding example (31), diluted 1:400in a water carrier, was applied by spray nine times, at two-weekintervals, to peach and nectarine cultivars during the growing season.The results against brown rot (Monolinia fructocola), compared tonontreated trees, is presented below.

    ______________________________________                                                         % Fruit Affected                                                              Peach Nectarine                                              ______________________________________                                        At harvest (treated)                                                                              1       3                                                 At harvest (untreated)                                                                           15      43                                                 Five days later (treated)                                                                         3       6                                                 Five days later (untreated)                                                                      60      67                                                 ______________________________________                                    

Example 33

The DDBSA/Cu-8-Q solution of Example 31 was tested in vitro against amajor turf pathogen, Helminthosporium vagans, via a standard agar plateculture technique, with these results:

    ______________________________________                                                    Fungus Colony Diameter                                            ______________________________________                                        1:6700 use dilution                                                                         1            mm                                                 in water carrier                                                              1:3350 use dilution                                                                         0                                                               in water carrier                                                              Control       21           mm                                                 ______________________________________                                    

The results demonstrate very high efficacy in controlling this importantpathogen. Complete control of H. vagans was achieved in this assaybetween 3.7 and 7.5 ppm of Cu-8-Q.

As illustrated in the examples to follow, the compositions of thisinvention have high efficacy against a broad spectrum of bacteria thatare pathogenic to mammals and plant life, that contribute to reducedwater quality, that cause deterioration of foodstuffs, that degrade abroad range of manufactured and natural materials and products, andwhich generate toxic metabolites (bacteria-toxins) that are among themost poisonous substances known to man.

Of particular interest is high efficacy against Gram-negative as well asGram-positive microorganisms. Few antibacterial materials now availableare effective against the Gram-negatives and still fewer provideeconomical control of them. A number of available antibacterials toxicto Gram-negative organisms have practical limitations which severelyrestrict use, including high mammalian toxicity, phytotoxicity,corrosiveness to skin and a variety of materials, strong odor, strongcolor, high volatility, low or erratic shelf stability, low ornonexistent residual activity, and prohibition of use at elevatedtemperatures.

The basic significance in the need for Gram-negative control lies in thefact that this bacterial category includes a number of widespread,virulent pathogens which are difficult to impossible to control withpresently available antibiotics, notably Pseudomonas sp. typified byPseudomonas aeruginosa PRD-10, the standard strain in the United Statesfor evaluation of antibacterials for mandatory Gram-negative controlapplications.

The compositions herein disclosed eliminate or substantially reducethese use limitations inherent in many other germicides. Thecompositions are quite unique in having strong Gram-positive andGram-negative activity combined with broad versatility of formulationand use plus a high degree of safety (low toxicity and zero to low skinand eye irritation). Add to this the high efficacy, broad spectrumantifungal activity of the compositions of this invention and theresulting range of toxicity to target organisms and safety to man, themost sensitive of hosts, is unique indeed.

The balance of toxicity provided by this invention to Gram-positive,Gram-negative and fungal microorganisms has special value in the broadconsumer field of skin deodorancy. Present antibacterials suffer fromthe fact that they are effective primarily against Gram-positives,allowing Gram-negative and fungi overgrowth, a condition considereddangerous by many authorities.

Example 34

The DDBSA/Cu-8-Q solution of Example 25 was tested, along with a numberof well known antimicrobial agents, against a broad spectrum screen ofeconomically important Gram-positive and Gram-negative bacteria. Allantimicrobial agents were incorporated in the agar bacterial growthmedia according to standard microbiological practices. The bacterialspecies were grown in nutrient broth; 24-hour cultures, the inoculum,then were streaked onto the nutrient agar plates containing the testantimicrobials. After a 24-hour incubation at the appropriatetemperature, the plates were rated for presence or absence of bacterialgrowth.

Minimum bactericidal concentrations for each of the tested agents arestated in the following tabulation of results in parts per million (ppm)of active ingredient as defined in the description of each agent.

    __________________________________________________________________________                    Antimicrobial Agent                                                           (ppm* of active ingredient)                                   Bacteria (ATCC No.)                                                                           A   B    C  D  E   F     G                                    __________________________________________________________________________    Gram-positive:                                                                Bacillus cereus 1   100  --  7 8    5-10 --                                   Bacillus lichenforms (27326)                                                                  1   100  --  7 8   2-5   --                                   Bacillus megaterium (27327)                                                                   1   100  --  7 8   --    --                                   Bacillus subtilis (37328)                                                                     1   100  -- 750                                                                              8   --     3                                   Micrococcus flavus (10240)                                                                    1   100  --  7 8   --    --                                   Mycobacterium phlei (15610)                                                                   1    10  --  7 8   --     3                                   Staphylococcus aureus (6538)                                                                  1   100  2083                                                                              7 8   1-3    3                                   Gram-negative:                                                                Alcaligenes faecalis (337)                                                                    10  1000 -- 750                                                                              80  --    --                                   Alcaligenes marshalii (21030)                                                                 104 100  --  7 8   --    --                                   Esherichia coli (11229)                                                                       104 10,000                                                                             -- 750                                                                              80  250-500                                                                             165                                  Flavobacterium arboresceus (4358)                                                             10   10  4166                                                                              7 8   --    --                                   Klebsiella pneumoniae (4356)                                                                  10  10,000                                                                             -- 750                                                                              8   --    --                                   Proteus vulgaris                                                                              10  1000 -- 750                                                                              800 --    --                                   Pseudomonas aeruginosa (15442)                                                                104 1000 4166                                                                             750                                                                              800 1000-2500                                                                           165                                  Salmonella cholerasuis (10708)                                                                104 1000 -- 750                                                                              80  250-500                                                                             165                                  Salmonella typhi (6539)                                                                       104 1000 2083                                                                             750                                                                              80  --    165                                  __________________________________________________________________________     *stated value of "1" means 1 or less?                                         A = the DDBSA/Cu8-Q solution of Example 25 with the active ingredient         expressed in terms of Cu8-Q.                                                  B = DDBSA.                                                                    C = phenol                                                                    D = Betadine, an iodine/polyvinylpyrrolidone complex containing 0.75%         iodine. The active ingredient is iodine.                                      E = Alkyl dimethyl ammonium chlorides (61% C.sub.12, 23% C.sub.14, 11%        C.sub.16 and 3% C.sub.10).                                                    F = sodium pentachlorophenate                                                 G = 2,3,5trichloro-4-propylsulfonyl pyridine.                            

These data demonstrate the high efficacy of the composition of Example25. On the basis of the average of the efficacies against all the testorganisms, Composition A is 45 times superior to Composition B; 88 timesbetter than Composition C; 10.7 times better than Composition D; and 3.5times superior to Composition E.

On the basis of the average of the efficacies against the three testbacteria (Staphylococcus aureus, Salmonella cholerasuis and Pseudomonasaeruginosa PRD-10) required by the Environmental Protection Agency of a"hospital grade" disinfectant, Composition A is 10 times better thanComposition B; 7.2 times better than Composition D; and 1.6 times betterthan Composition E.

Example 35

The composition set forth below was prepared by previously describedprocedures:

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

Isopropanol 32.00 parts by weight

DDBSA 40.00 parts by weight

Water (demineralized) 25.22 parts by weight

When evaluated as a bactericide by the AOAC Use Dilution Method (12thEdition, 1975), 10 ring carriers per organism, the following resultswere obtained (A=subculture and B=resubculture):

    ______________________________________                                                     Use Dilution                                                                            Negative Positive                                                   in Water Carrier                                                                        A      B     A    B                                    ______________________________________                                        Staphylococcus aureus                                                                        1:1000      10     10  0    0                                  Salmonella cholerasuis                                                                       1:1000      10     10  0    0                                  (PRD-10)                                                                      Pseudomonas aeruginosa                                                                       1:400       10     10  0    0                                  Aerobacter aerogenes                                                                         1:400       10     10  0    0                                  ______________________________________                                    

A ten-minute kill is required against the first three pathogens for saleas a hospital grade disinfectant. Efficacy against the fourth organism,a major cause of slime in recirculated cooling water systems and pulpand paper mills, demonstrates utility of the composition as a slimicide.

Example 36

This composition was prepared and tested at one use dilution, 1:50 inwater carrier, against the causal agent of potato ring rot bacteria(Corynebacterium sepedonicum):

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

Infected potato seed readily contaminate potato seed cutters, sacks,bins, cellars, trucks and planting equipment with the highly infectiousring rot bacteria. The result may be infected potato plants, tubers andreduced yields.

The test procedure consisted of dipping unpainted, planed wood laths(6") into a slurry of infected ring rot tuber tissue, allowing excessslurry to drain off (3-5 minutes) and then spraying the contaminatedlath with the test antibacterials. Three to five minutes later, healthyNorgold Russet potato seed pieces were rubbed vigorously against bothsides of the contaminated and antibacterial-treated laths. The processwas repeated using laths not contaminated with C. sepedonicum buttreated with the test antibacterial agent. The rubbed seed pieces werestored in bags and later planted at the appropriate time.

In addition to the composition of the invention, untreated controls, 20%Clorox (1.05% sodium hypochlorite in water), formaldehyde (37% formalindiluted 1:120 in water) and Roccal (benzalkonium chloride or sephiranchloride) diluted with water to 800 ppm concentration were tested. Theresults of the test are tabulated below and refer to plants and tubersproduced from the tubbed test seed pieces.

    __________________________________________________________________________             Ring Rot                                                                             % Plant                                                                            % Ring Rot                                                                           % Ring Rot                                                                           Yield                                      Antimicrobial                                                                          Contaminated                                                                         Stored                                                                             Plants Tubers cwt/acre                                   __________________________________________________________________________    None (control)                                                                         Yes    98   23     8      493                                        None (control)                                                                         No     95   0      0      609                                        DDBSA/Cu-8-Q                                                                           Yes    98   0      2      631                                        DDBSA/Cu-8-Q                                                                           No     100  0      0      602                                        20% Clorox                                                                             Yes    98   20     9      500                                        20% Clorox                                                                             No     98   0      0      602                                        Roccal   Yes    98   20     9      515                                        Roccal   No     98   0      0      638                                        __________________________________________________________________________

The composition of this example demonstrates superior control of thering rot bacterium. Other species of the genus Corynebacterium arecausal agents of disease in man and a variety of plant life.

Example 37

The composition below was prepared and tested for speed and range ofantibacterial activity, in the absence and presence of organic matter(blood) for use in hospital disinfection, cold sterilization andantisepsis.

Oxine 4.1 parts by weight

Copper hydrate 1.4 parts by weight

DDBSA 65.0 parts by weight

Propylene glycol methyl ether 29.5 parts by weight

Many antimicrobial agents are partially or totally deactivated in thepresence of organic matter, constituting a severe limitation toeffectiveness of such agents for a number of uses such as woundantisepsis and medical instrumentation and surface disinfection wherelarge amounts of organic matter often are encountered and sometimes areunavoidable.

The AOAC Use Dilution Confirmation Test (12th Edition, 1970) wasmodified as follows:

(a) The test temperature was 37° C.

(b) The ring carriers were soaked in sheep blood for two hours,air-dried for one hour, then contaminated with the test pathogen.

(c) The contaminated rings were contacted with the test antibacterialagent for 30-second, one-minute and three-minute periods.

The results are set forth in the following table, in which:

0=no growth in 10 of 10 tubes tested

1=growth in 1 of 10 tubes tested

2=growth in 2 of 10 tubes tested

3=growth in 3 of 10 tubes tested etc.

    __________________________________________________________________________                Use Dilution in                                                                       In Absence of Blood                                                                       In Presence of Blood                          Test Pathogen                                                                             Water Carrier                                                                         30 sec.                                                                           1 min.                                                                            3 min.                                                                            30 sec.                                                                           1 min.                                                                            3 min.                                __________________________________________________________________________    Staphylococcus aureus                                                                     Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 6538) 1:10    0   0   0   0   0   0                                                  1:100  0   0   0   3   6   3                                     Salmonella typhi                                                                          Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 6539) 1:10    0   0   0   0   0   0                                                 1:00    0   0   0   0   0   0                                     Pseudomonas aeruginosa                                                                    Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 15442)                                                                              1:10    0   0   0   10  10  0                                                  1:100  0   0   0   10  3   3                                     __________________________________________________________________________

These results indicate that the test composition is capable of rapidantibacterial action in the presence of substantial amounts of organicmatter against the three human pathogens generally considered asdefinitive for antibacterial efficacy evaluation.

Example 38

The composition of Example 28 was prepared for evaluation as a skindegerming agent against resident and transient flora. Six subjects weretested using the Modified Prices Multiple Basin Technique which measuresreduction of skin flora as a percentage of that achieved by washing thehands with unmedicated soap. Bacterial counts were taken from the first,fourth and fifth basins. The counts from the first basin represent thetransient bacterial flora and that of the fourth and fifth basins theresident flora. Prior to the test, none of the subjects used a medicatedsoap for one week.

The results set forth in the following table demonstrate a very highorder of efficacy for the test composition for critical degerming usessuch as a surgical scrub for operating room personnel and skinpreparation at the surgical site.

    ______________________________________                                                      Unmedicated Soap                                                                            Test Composition                                                Average No. of                                                                              Average No. of                                                                           % Re-                                  Subject                                                                             Basin   Organisms/Basin                                                                             Organisms/Basin                                                                          duction                                ______________________________________                                        1     1       2,500,000     60,000     97.6                                         4       1,900,000     25,000     98.7                                         5       1,300,000     15,000     98.8                                   2     1       1,700,000     30,000     98.2                                         4       1,100,000     20,000     98.2                                         5         800,000      1,000     99.9                                   3     1         800,000     40,000     95.0                                         4         600,000     20,000     96.7                                         5         500,000      1,000     99.8                                   4     1       2,000,000     50,000     97.5                                         4       1,000,000      1,000     99.9                                         5         800,000      1,000     99.9                                   5     1       1,500,000     40,000     97.3                                         4         800,000      1,000     99.9                                         5         500,000      1,000     99.8                                   6     1       1,900,000     50,000     97.4                                         4         800,000     15,000     98.1                                         5         520,000      1,000     99.8                                   ______________________________________                                    

Example 39

Oxine 2.08

Copper hydrate 0.70

Nonyl phenol/EO surfactant* 20.00

DDBSA 45.00

Isopropanol 15.00

Water (distilled) 17.22

The above composition was prepared by the procedure already describedand evaluated for efficacy against ciliated protozoan and two types ofviruses.

    ______________________________________                                        Hemaglutination Assays                                                                 HA Titre                                                             Virus      Untreated Treated (1:50)*                                                                           Treated (1:200)                              ______________________________________                                        Adenovirus 128       0           0                                            Newcastle Dis-                                                                           512       0           0                                            ease virus                                                                    ______________________________________                                         (*1:50 and 1:200 use dilutions of composition in a water carrier in           contact with virus suspensions for 15 minutes)                           

The HA titre is a measure of the number of infectious virus particlespresent in the test suspension.

Plaque Assays

Via the same procedure as above, the untreated virus suspensionscontained 6.4×10⁴ pfu/ml of Adenovirus virus particles and 21×10⁵ pfu/mlNewcastle Disease virus particles respectively. After treatment with the1:50 and 1:200 use dilutions, readings of 0 pfu/ml were obtained. Eachpfu represents one infectious virus particle. A zero pfu readingrepresents total inactivation of the infectious virus.

Protozoan inhibition

Inhibition of growth of ciliated protozoan (Tetrahymena) in pond waterwas obtained at a 6 ppm concentration (based on Cu-8-Q) of the abovetest composition of DDBSA and Cu-8-Q after 6-hour and 72-hourcontacttimes. The 6 ppm reading represents the MIC (Minimum InhibitoryConcentration). These results demonstrate high efficacy of the testcomposition against the test microorganisms.

Example 40

In some instances, it may prove advantageous to include othermicrobicides in a given formulation to increase the over-all spectrum ofantimicrobial activity. Such additional microbicides need notnecessarily be of the type thus far described in this specification. Forexample, when treating green lumber to inhibit sapstain or mold, it issometimes desirable, to get broader protection, to include achlorophenol such as pentachlorophenol, tetrachlorophenol, or2,4,5-trichlorophenol, in the composition of this invention. Also, toprovide additionally against insect attack, it is within the scope ofthis invention to include insecticides such as Lindane or DDT.

Further, it has been found that boric acid can be added to the class ofcompositions of this invention with beneficial microbiocidal results:

Copper hydrate 0.035

8-hydroxy quinoline 0.104

Methanol 0.736

DDBSA 1.630

Orthoboric acid 2.500

Water 94.995

The above concentrate, prepared as previously described, was diluted 1:9with water and fresh, rough-sawn, green southern yellow pine lumber wastreated by 10-second dip immersion. Sample boards were placed, togetherwith an equal number of untreated control boards and other testspecimens in a chamber maintained at 75° F. and 70% relative humidityfor 28 days.

    ______________________________________                                                              % Stain and Mold                                        ______________________________________                                        DDBSA/Cu-8-Q composition of Example 5                                                                  6                                                    1:200 use dilution in water                                                   DDBSA/Cu-8-Q/orthoboric acid solution                                                                  7                                                    described immediately above                                                   DDBSA/Cu-8-Q composition of Example 5                                                                 14                                                    1:400 use dilution in water                                                   Orthoboric acid, 0.50% in water                                                                       62                                                    Orthoboric acid, 0.25% in water                                                                       86                                                    Untreated control boards                                                                              88                                                    ______________________________________                                    

Example 41

Some of the compositions of this invention exhibit unexpectedinsecticidal activity when compared to the conventional solubilizedCu-8-Q compositions and when compared to a known insecticide(pentachlorophenol). Against termites in a soil burial test in Memphis,Tenn., the following compositions were evaluated:

(a) Example 12, diluted with water to a 0.25% Cu-8-Q content;

(b) Example 18, diluted with mineral spirits to a 0.25% Cu-8-Q content;

(c) Cunilate 2174, diluted with mineral spirits to a 0.25% Cu-8-Qcontent; and

(d) A 5.0% pentachlorophenol solution in mineral spirits containing 4%propylene glycol ether to provide sufficient pentachlorophenolsolubility and to prevent sublimation from the wood.

Dry southern yellow pine stakes, 3/4" square×24" long, weredip-impregnated with the test solutions, allowed to dry for one week,and then buried to a depth of 12" in the ground for 15 months, at whichtime these results were observed:

    ______________________________________                                                        Solution Pickup                                                                           Termite                                           Treatment       (lbs/ft.sup.3)                                                                            Rating*                                           ______________________________________                                        None (control stakes)                                                                         --          36                                                Example 12      1.79        83                                                Example 18      1.13        80                                                5% pentachlorophenol                                                                          1.28        84                                                solution                                                                      Cunilate 2174   1.26        56                                                ______________________________________                                         (*Termite rating:                                                             0 = stakes totally destroyed                                                  100 = stakes unattacked)                                                 

Both compositions of this invention exhibited termite controlessentially equal to that of the pentachlorophenol solution anddefinitely superior to both the untreated control stakes and thosetreated with Cunilate 2174.

Examples 42 to 50

As further evidence of the effectiveness of antimicrobials prepared inaccordance with this invention, a number of tests were conductedutilizing DDBSA as the disubstituted aryl compound of this invention asa solution with the below-listed microbicidal agents. A 1:200 usedilution in a water carrier was prepared from concentrates containing 65parts DDBSA, 30 parts methanol, and 5 parts of the antimicrobial agent.Fresh-cut green pine test boards were dip-treated and evaluated forstain and mold after 30 days in the aforementioned constant atmospheretest chamber:

    ______________________________________                                                                       % Mold                                         Example Antimicrobial Agent    and Stain                                      ______________________________________                                        42      Cu-8-Q                  3                                             43      2-(4-thiazolyl)benzimidazole                                                                         14                                             44      cis-N--(trichloromethyl)thio-                                                                        23                                                     4-cyclohexane-1,2-dicarboximide                                       45      diiodomethyl-para-tolyl sulfone                                                                       8                                             46      para-chlorophenol diiodomethyl sulfone                                                                6                                             47      2-n-octyl-4-isothiazolin-3-one                                                                       10                                             48      2-benzisothiazolin-3-one                                                                             14                                             49      Mergal BCM              2                                             50      8-hydroxy quinoline    10                                             ______________________________________                                    

Example 51

The following composition was prepared and evaluated for control ofpineapple disease of sugar cane (Ceratocystis pilifera):

2-(methoxy-carbamoyl)-benzimidazole 4.0

DDBSA 70.0

Propylene glycol methyl ether 26.0

Sugar cane seed was treated with this solution as diluted with a watercarrier. Seed also was treated with benomyl, triophanate methyl,Panoctine (9-aza-1,17-diquanidinoheptadecane triacetate), hot water andcold water. The results are tabulated below:

    ______________________________________                                                   Concentration, ppm                                                                          % Emergency                                                     of active ingredients (1)                                                                   Inoculated (2)                                       ______________________________________                                        DDBSA/2-(methoxy-                                                                           50             48                                               carbamoyl)-benzimi-                                                                        100             54                                               dazole       200             53                                               Thiophanate methyl                                                                          50             55                                                            150             51                                                            300             49                                               Panoctine     50             48                                                            100             48                                                            200             53                                               Benomyl      150             50                                               Hot water     0              36                                               Cold water    0              27                                               ______________________________________                                         (1) The active ingredient for the composition of this example is stated i     terms of the benzimidazole content; all others are stated in terms of the     listed chemical compound.                                                     (2) Prior to planting, the seed was inoculated with the causal disease        organism, Ceratocystis pilifera. Emergence data was collected 56 days         after planting.                                                          

These results demonstrate the in vivo efficacy of the compositions ofthis example. Additionally noteworthy is the fact that, at the 27-daymark, the emergence rate was noticeably higher for the composition ofthis example as compared to all other treatments.

Example 52

The foregoing examples involve complexes between the disubstituted arylcompound and known antimicrobials. Another feature of the invention isthe discovery that some agents not ordinarily considered to beantimicrobial are effective when dissolved in the disubstituted arylcompounds of this invention. A case in point is phthalimide which is notoffered commercially as a fungicide and which Horsfall, in Principles ofFungicidal Action, describes as having very little fungicidal activity.Yet the composition described below exhibits excellent control of stainand mold fungi in green lumber.

Phthalimide 0.44 lbs.

DDBSA 0.88 lbs.

Sodium hydroxide 0.44 lbs.

Water 100.00 gallons

The sodium hydroxide was dissolved in one quart of water, thephthalimide then added and the mixture stirred until a clear solutionresulted. The DDBSA was then added with stirring, followed by thebalance of the water. The composition was evaluated by treating green,rough-sawn southern yellow pine boards. After two weeks' exposure:

    ______________________________________                                                         % Mold and Stain                                             ______________________________________                                        DDBSA/phthalimide solution                                                                        0                                                         Untreated control boards                                                                         45                                                         ______________________________________                                    

It is theorized, and indicated by Horsfall, that phthalimide is anactive toxiphore, yet is essentially ineffective as an antimicrobialbecause of its low fat solubility.

According to the concept of this invention, when a solution is formedbetween phthalimide and the disubstituted aryl compound, the oleophilicsubstituent may lead the toxiphore into the microbial cell and act as anactive antimicrobial. Other active toxiphores, such as benzimidazole,which lack only fat solubility for antimicrobial activity, can beconverted by this same concept into active antimicrobials.

Example 53

High water hardness and/or high use dilutions can cause precipitation ofthe compositions of this invention which otherwise would remain in truesolution in water. In some instances of use, it is desirable to maintainthe true solution character of the diluted composition. It has beenfound that a number of modifications to the composition will eithereliminate or delay the formation of solid matter in the use solution,the presence of such particulate matter being evidenced generally by acloudy appearance. Among the more effective of such modifying agents are(1) partial or total replacement of the diluting water with a loweralcohol such as methanol, ethanol or isopropanol, or (2) additional ofnonionic surfactants such as alkyl phenol ethoxylates.

The following compositions were prepared:

    ______________________________________                                                           A    B                                                     ______________________________________                                        Oxine                 2.07  0.72                                              Copper hydrate        0.70  0.25                                              DDBSA                40.00  14.00                                             Isopropanol          20.00  7.00                                              Distilled water      37.23  52.03                                             Octyl phenol ethoxylate                                                                            --     26.00                                             ______________________________________                                        (9 EO)                                                                        ______________________________________                                    

Composition A exhibited solution clouding when diluted 1:300 with watercontaining 120 ppm hardness (total dissolved solids), whereasComposition B did not. In terms of the Cu-8-Q/DDBSA content, a 1:300dilution of Composition B is the equivalent of a 1:857 dilution ofComposition A.

Example 54

The alkyl aryl sulfonic acids of this invention, typified by DDBSA, arestrong acids and, as such, are harmful to many substrates and, inparticular, are highly corrosive to human skin and capable of producingsevere irritation and burns. The addition of metal-oxine compounds toDDBSA, as described herein, reduces the corrosive action of DDBSAsignificantly, even in small amounts. This is entirely unexpected and noadequate explanation for this fact has yet been found.

The following compositions were prepared (all parts by weight):

    ______________________________________                                                    A    B          C      D                                          ______________________________________                                        Oxine         8.2    4.1        2.1  --                                       Copper hydrate                                                                              2.8    1.4        0.7  --                                       DDBSA         59.0   59.0       40.0 59.0                                     Propylene glycol                                                                            30.0   35.5       57.2 41.0                                     methyl ether                                                                  ______________________________________                                    

These compositions were tested for skin irritation by rubbing 2 ml ofeach onto the hands of six test subjects. After 60 seconds, CompositionsA, B and C were rinsed off the hands with water. None of the testsubjects noted any adverse effect such as stinging, burning, itching orwarming during the test or thereafter. The results with Compositions Dand E were observably different. With 5 seconds after application, alltest subjects noted a strong heating, burning sensation that requiredimmediate and thorough removal with running water. A relatively mildstinging sensation was noted thereafter by four of the six test subjectsfor periods of about thirty minutes to two hours.

The compositions of this invention exhibit a unique combination ofcleaning effectiveness and mildness heretofore unknown in cleaningagents. More specifically:

Effectiveness--Equal to superior to the best traditional types ofcleaning agents. Cleaning efficacy, particularly notable on metals,concrete, brick, porcelain and grouting, is applicable both to inanimatesubstrates and human uses.

Mildness--Even at concentrations much higher than normal use dilutions,no adverse effects upon the hose substrate are noted when employed intypical cleaning procedures. Such substrates include painted surfaces,most metals, concrete, brick, porcelain enamel, wood, plastics, wool,leather, glass, cotton, linen, synthetic fabrics and the like. Thisunusual mildness and lack of irritation is observed also in human uses,even upon the most delicate skin areas, eyes and mucous membranes. Ondilicate body surface areas, the compositions proved significantly lessirritating than Ivory Soap, a long-time standard for mildness.

High cleaning efficacy for general purpose uses coupled with unusuallylow substrate damage potential to inanimate substrates and lack ofirritation to humans and animals is uncommon in low pH products andunusual even in conventional cleaners in the relatively neutral pH range(6 to 8). By comparison, the pH of use concentrations of the compositionof the invention most generally range from about 1.5 to about 2.5.

Historically, cleaning agents have been alkaline, and the higher thealkalinity, the greater is the effectiveness and harshness. In recentyears, a trend toward mildly acid chances (pH 5 to 6) for certainspecialty uses--hair shampoos, for example--has been underway, andhighly acidic and oxidizing cleaning materials are traditional forcertain highly specialized applications such as metal, dairy equipmentand toilet bowl cleaning. In these cases, the acidity serves a specificpurpose, such as removal of oxide (metals), hardened milk deposits(dairies) and iron discoloration (toilet bowls). Such products, however,damage most substrates and are much too corrosive for human use. The lowpH compositions disclosed herein not only are contrary to traditionalconcepts, but exhibit an extremely broad range of consumer, commercialand industrial uses ranging from a vaginal douche at one extreme to castiron engine block cleaning at the other end of the spectrum. In certainspecialized applications where highly acid cleaners have long been used,the compositions will provide equal to superior cleaning action withoutthe associated dangers. For example, the compositions will clean mostleather surfaces more effectively than an oxalic acid/water solution, arecommended leather cleaner which is toxic, and corrosive to humans,animals and most substrates.

It is within the scope of this invention to modify the disclosedcompositions to improve performance or alter physical properties andmeet final product needs for a wide range of end uses in many fields,including product material and process preservation, medical, animalhealth care, water treatment, plant disease control, disinfection,sanitization and cleaning, cosmetics and toiletries.

In many instances, the compositions of the invention constitute only aminor portion of the final product formulation, in substantial measurebecause the high efficacy requires only small amounts. The rule for useof other ingredients in the disclosed compositions is simple andobvious--namely, such ingredients must be compatible with thecompositions and must not deactivate the antimicrobial activity below ausable level. Among the types of usable and desirable other ingredientsare wetting agents, detergents and surfactants, emollients, otherpesticides, thixotropes, film-formers, foam-builders and antifoamers,soil antideposition and antiredeposition agents, wet slip enhancers,fillers, colorants, taste modifiers, odor masking agents and fragrances,fire retardants, corrosion inhibitors, chelators for undesirable metalsincluding those causing water hardness, and acidification andalkalization agents. Generally, the compositions of this invention mustbe maintained, at the desired use dilution and at the time of use orincorporation into another composition, material or product, at a pH ofabout 3.5 or below. The preferred pH, at least when metal oxines areused, is below 2.8.

The antimicrobial compounds of this invention are effective to controlodors caused by biological activity. Since many of the compounds becomeaffixed to many substrates, their value as an antimicrobial and orderdestroyer will remain for a prolonged period of time and even survivemany washings of certain substrates, such as garments.

The physical form of the compositions of this invention can vary widely.The most commonly desirable form is a low viscosity liquid--the form ofthe examples given above. But other forms fall within the scope of theinvention and may be preferred for certain end uses, including solids,powders, high viscosity liquids, ointments and creams, and gels. All ofthe foregoing examples consist of compositions that are true solutions,both in concentrate and use-diluted form. Such true solutioncompositions generally are preferred for the majority of cases for anumber of practical handling and application reasons. However,compositions that are in emulsion form or which exist as liquid or solidsuspensions are within the scope of this invention and have definiteutility.

The compositions described above will hereinafter be referred to as the"compositions of section 1".

SECTION 2

We have also discovered that the antimicrobial activity of knownphenolic antimicrobials can be improved by mixing a minor amount of suchknown phenolic antimicrobials with a major amount of a solution preparedby solubilizing a non-phenolic antimicrobial agent as set forth insection I with a disubstituted aryl compound having a hydrophilic and anoleophilic substituent (as described in section I hereinabove). In onepreferred embodiment said second antimicrobial agent is anorganometallic compound (as described in section I above) such as ametal chelate of oxine and the disubstituted aryl compound is alkylbenzene sulfonic acid (most preferably DDBSA in which the alkyl chainpredominates in C₁₀ to C₁₃.)

Certain phenolic compositions are known to the prior art that haveefficacy against certain microbials including fungi and Gram-positiveand Gram-negative bacteria. Many of these phenolics are falling intodisfavor because of their relatively high toxicity toward animal andplant life. This is particularly true since, for many applications, anundesirably large amount of phenolics must be used to achieve a desireddegree of antimicrobial activity against certain microbes. Theutilization of phenolic antimicrobials is further limited in that theyare frequently limited in the spectrum of microbes against which theydisplay effective antimicrobial activity.

Accordingly, a further object of this invention is to improve theefficacy of phenolic antimicrobial agents.

A related object of this invention is to formulate phenolicantimicrobial compositions in a manner in which effective antimicrobialactivity can be achieved with a minimum quantity of the phenolics.

Another object of this invention is to widen the spectrum of microbesover which phenolic compositions display effective antimicrobialactivity.

These and other objects of this invention are achieved by including aminor amount of an antimicrobial phenolic composition in a solutioncomprised of a non-phenolic antimicrobial composition as set forth insection I and a disubstituted aryl compound as set forth in section I.

This embodiment of our invention is illustrated by the followingexamples:

Example 1

The following two compositions were prepared (amounts are weightpercent):

    ______________________________________                                                         A    B                                                       ______________________________________                                        Oxine               2.05  2.05                                                Copper hydrate      0.07  0.70                                                DDBSA              40.00  40.00                                               Isopropanol        32.00  32.00                                               Distilled water    25.25  15.25                                               Orthophenyl phenol --     10.00                                               ______________________________________                                    

Both compositions were tested against the Gram-positive Staphylococcusaureus bacterium in accordance with the AOAC Use Dilution ConfirmationMethod with these results:

    ______________________________________                                        Use Dilution      No. of Tubes Tested                                         in Water          Positive*                                                                              Negative*                                          ______________________________________                                        A     1:1000          0        10                                             A     1:1250          1         9                                             B     1:1250          0        10                                             B     1:1500          1         9                                             ______________________________________                                         (*positive  growth; negative  no growth)                                 

These results indicate that efficacy of Composition A was improved byabout 20-25% by addition of 10% orthophenyl phenol to Composition A(forming Composition B). By calculation, using technical bulletinspublished by the producer of orthophenyl phenol for disinfectantformulation, the efficacy improvement should have been about 4%. Inshort, the orthophenyl phenol addition actually improved efficacy by afactor of five to six times the calculated theoretical improvement.

Example 2

Composition C was prepared as follows (amounts are weight percent):

Oxine 2.05

Copper hydrate 0.70

DDBSA 40.00

Isopropanol 32.00

Distilled water 15.25

4-chloro-2-phenyl phenol 10.00

Composition C was tested and compared with Composition A of Example 1against the standard Gram-negative bacterium Pseudomonas aeruginosaPRD-10 in accordance with the aforementioned AOAC Use Dilutionprocedure, with these results:

    ______________________________________                                        Use Dilution      No. of Tubes Tested                                         in Water          Positive*                                                                              Negative*                                          ______________________________________                                        A     1:500           1         9                                             C     1:750           0        10                                             ______________________________________                                         (*positive  growth; negative  no growth)                                 

Reference tests on antibacterials and the manufacturer's technicalliterature on 4-chloro-2-phenyl phenol indicate that this phenol hasvery low activity against P. aeruginosa (a phenol coefficient of "lessthan 10"). Even assuming a phenol coefficient of as high as 10, theamount of 4-chloro-2-phenyl phenol in Composition C should haveimproved, by calulation, the use dilution efficacy of Composition C byabout 4% over that of Composition A which contains no phenol. Instead animprovement of an indeterminate amount in excess of 50% was obtained,indicating that the addition of the phenol to Composition A improved itsantibacterial activity out of all proportion to the amount of phenoladded.

The antifungal efficacy of these phenolics is improved by formulation inaccordance with this invention. Orthophenyl phenol,2,3,5-trichlorophenol, tetrachlorophenol and pentachlorophenol, forexample, exhibit antifungal efficacy improvement significantly higherthan would be expected when formulated conventionally, especially foruse in a water carrier where customary formulation methods employ awater-soluble alkaline salt of such phenols, such as the sodium orpotassium salts.

The quantity of phenolic antimicrobial added to the antimicrobialsolution is not critical and can be varied depending on themicroorganism that it is desired to control and the permitted toxicityof the total composition. As noted in the examples, a 10% inclusion of aphenolic is quite effective and can vary over a wide range, although5-20% is generally preferred.

SECTION 3

We have also discovered a method for reducing the skin and eyeirritation of alkyl aryl sulfonic acids (as set forth in Section 1). Ina preferred embodiment, the irritation-reducing agent is anorganometallic antimicrobial agent (as set forth in section I) which issolubilized in the alkyl aryl sulfonic acids and which in additionprovides for antimicrobial efficacy. The irritation of the solution canfurther be reduced by including a second irritation-reducing agent suchas polyvinyl pyrrolidone or selected surfactants such as ethoxylated andprothoxylated long-chain aliphatic alcohol type surfactants, ethoxylatedalkyl phenol type surfactants or a sulfosuccinate of a higher fatty acidmonoethanolamid. The following Examples are illustrative:

Example 1

A commercial grade of undiluted DDBSA was poured onto and spread overthe hands of several persons. An almost immediate warm and uncomfortablesensation was noted, causing the persons to flood their hands with waterto remove the DDBSA.

The experiment was repeated, using DDBSA into which had been dissolved10% by weight of copper-8-quinolinolate (Cu-8-Q). No immediate sensationof discomfort was felt as had been the case with the unmodified DDBSA.

Example 2

The following composition was prepared:

Oxine 2.05 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Isopropanol 15.00 parts by weight

Water 42.75 parts by weight

A second test solution also was prepared wherein five parts of the waterin the above composition was replaced by an equal amount of polyvinylpyrrolidone (PVP) solution in water (GAF's NPK-60).

The two compositions were tested for skin irritation by placing twodrops of one composition on the skin at the inside of one elbow of fivetest subjects and two drops of the other composition on the same spot onthe other elbow of each subject. In all cases, the composition wassmeared over about a one-half square inch of skin and the subjects'reactions were noted over a 20-minute test period.

The first composition (no PVP) was described variously as "burning,""stinging," "tingling" and "warming". The second composition (containingPVP) was described by the subjects over the range of noticeably milderskin sensation to none at all.

A third composition was prepared, identical to the second except thatthe PVP content was increased to twenty parts, again replacing an equalamount of water. Tested as before, no skin sensation was reported by anyof the test subjects.

Example 3

These compositions were prepared (all parts by weight):

    ______________________________________                                                         A    B                                                       ______________________________________                                        Oxine               4.1   4.1                                                 Copper hydrate      1.4   1.4                                                 DDBSA              60.0   60.0                                                Isopropanol        34.5   24.5                                                PVP (NPK-60)       --     10.0                                                ______________________________________                                    

The compositions were tested on three subjects for skin irritation byspreading two drops of each composition over a one square inch area ofskin just below one eye of each test subject and the other compositionon the same spot beneath the other eye.

Composition A became uncomfortable on the three test subjects within oneto three minutes and was removed. Composition B exhibited no sensationof discomfort to much milder sensation than Composition A for theten-minute duration of the test.

Example 4

The first composition of Example 1 was prepared containing 30% PVPsolution. When tested in accordance with the procedure of Examples 1 and2, no sensation of skin discomfort was noted by any of the testsubjects.

Example 5

It further has been discovered that a range of ethoxylated andpropoxylated long-chain aliphatic alcohol type surfactants andethoxylated alkyl phenol type surfactants provide noticeable skinirritation reduction for compositions of the type disclosed in previousexamples, using the same test procedures. These nonionic surfactanttypes do not appear, however, to be as effective as PVP, but have provedparticularly useful for many applications where the detergencycharacteristics of these additives to the basic compositions of theinvention are desirable. Examples of useful surfactants in these classesinclude phenols with C₈ through C₁₂ alkyl side chains, alcohols with C₁₀to C₂₂ chain lengths and ethylene oxide and propylene oxide adductsthereon from about 4 to about 100. Suitable alkyl phenols include octylphenol, nonyl phenol and dodecyl phenol plus dinonyl and didodecylphenols.

By way of example, the first composition of Example 2 was preparedexcept that 20 parts of water were replaced with an equal amount ofoctyl phenol ethoxylate (9 EO). Tested as before, this compositionexhibited distinctly less skin irritation than without the octyl phenolethoxylate.

Another additive found to reduce the irritation of the compositions ofthe invention is a sulfosuccinate of a higher fatty acid monoethanolamidsold by Cyclo Chemicals Corporation under the designation CyclopolSBR-3. Significant improvement in irritation characteristics wasobserved using 3%, 10% and 20% replacements of water in the firstcomposition of Example 2 with this material, which has a 40% activeingredient content.

It should be noted that no critical lower or upper limits have beennoted as to the amounts of these irritation reduction agents which maybe used in the practice of this invention. Generally, increased amountsproduced greater reductions in irritation. The quantity added may bevaried not only to obtain the desired irritancy reduction, but also toobtain other desired properties in the final formulation.

SECTION 4

We have also discovered a method for materially increasing thesolubility of compounds having insecticidal properties. Other compoundsheretofore recognized as having only antimicrobial activity becomeuseful for insecticidal purposes when solubilized, particularly throughthe use of a disubstituted aryl compound described in Section 1,particularly an alkyl benzene or naphthylene sulfonic acid.

Thus, our invention also includes insecticides which may be madewater-soluble, at least in concentrated form, and which may, in some ofthe formulations display reduced toxicity towards mammalian and plantlife.

The compositions set forth in section I have been found to exhibit anunexpected degree of insect control. This has importance in a variety ofend uses, notably wood preservation, wherein there is little advantagein protecting wood from fungal decay if the wood is preserved only forinsects, such as termites, to destroy. In many areas of the world,including those with high decay rates, destruction of wood by termitesoccurs more rapidly than does fungal degradation.

It also has been found that the compositions set forth in Section 1 arecompatible with a broad range of well-known insecticidal chemicals inuse for a broad range of agricultural, medical, animal health care,product and material preservation, and micellaneous pest controlapplications. This discovery extends the end use range of thecompositions of Section 1 where insect control in addition to thatafforded by the composition itself is desired, or in those instanceswhere the basic composition provides no control of the target pests.Providing insect and antimicrobial control in one composition also hasboth economic and convenience advantages.

Entirely unexpected is our discovery that a number of standardinsecticides incorporated in the compositions of Section 1, includingDDBSA alone or in combination with an antimicrobial, form true solutionsin the formulation concentrates and, of far greater significance, truesolutions when water-diluted for use. Most insecticides arewater-insoluble and consequently must be formulated for use as wettablepowders, flowables, or as emulsifiable liquid concentrates. Generally,these products, when diluted for use with water as the carrier, formsuspensions or emulsions of mediocre stability, requiring frequentagitation to maintain an acceptable degree of dispersion in the carrier.True solutions are easier to use and provide more uniformity of coverageof the substrate or host organism for protection against the targetorganisms. True solutions also make practical certain end uses wheresuspensions and emulsions of inadequate stability and poor substantivityare not functionable. Such suspensions and emulsions, for example, willnot penetrate wood adequately. For long-term protection of wood for manyuses, deep impregnation is mandatory.

A number of additional standard insecticides form true solutions whenincorporated into the compositions of Section 1 in concentrated form,but form-stable colloidal emulsions when water-diluted for use. Suchemulsions for most uses offer all of the advantages of true watersolutions in terms of desired stability and ability to penetrate andadhere to substrates such as wood and tight-weave fabrics.

While water generally is the carrier of choice for preparing dilutions,other carriers have utility in certain instances, including hydrocarbonsand a variety of polar organic solvents.

A criterion for combining insecticides with compositions of the basicinvention is stability of the insecticide to acidic media. The amount ofinsecticide practically incorporatable into composition concentrates forsubsequent use dilution in true solution or stable emulsion form dependsupon a number of factors including inherent solubility characteristicsof the insecticide in the basic composition of Section 1 and the make-upof this basic composition. The larger the amount of DDBSA in said basiccomposition the larger the quantity of a given insecticide that may besolubilized in the basic composition. The ratio of insecticide to saidbasic antimicrobial composition is relatively noncritical and the choicein large measure depends upon the desired combination ofantimicrobial-to-insecticidal performance.

Among the useful insecticides that may be incorporated into thesolubilizing disubstituted aryl compounds of Section 1, either with orwithout antimicrobials according to Section 1, are carbaryl,methoxychlor, lindane, chlordane, malathion, parathion and methylparathion, toxaphene, dieldren, aldrin, endrin, heptachlor, baygon andcygon. TBTO (tributyl tin oxide) which is not a recognized insecticide,also has utility against marine wood borers.

In cases where antimicrobial action is not wanted, it is within thescope of this invention to incorporate the insecticide in thedisubstituted aryl compounds of Section 1 plus a diluent. However, someinsecticides seemingly exhibit reduced solubility characteristics in theabsence of a metal-oxine chelate according to Section 1.

An important area of use for the insecticide-antimicrobial compositionsdescribed in this section relates to the known usefulness of certaininsecticides for protection of wood in marine service against marineborers which attack and destroy wood rapidly. There are three importantspecies of wood-destroying borers in two classes: (1) Molluscan--Teredoand Martosia sp., and (2) Crustacean--Limnaria sp. It is near-axiomaticthat no one toxicant is effective against all three species, and it is afact that in certain tropical waters, no single wood impregnant hasprovided satisfactory durability. For example, some waters off Key WestFlorida are inhabited by combinations of marine borers which willdestroy a wood piling impregnated with 20 lbs of creosote per cubic footin five years, despite the fact that heavy creosote loadings in wood areconsidered to be the preservative of choice for marine applications theworld over. Additions to creosote of chlordane, dieldrin, and TBTO amongother insecticides is reported to substantially improve creosoted woodpiling durability in certain waters.

Accordingly, addition of these insecticides to the basic antimicrobialcomposition of Section 1 provides improved wood durability in marineenvironments. Additionally, our discovery allows use of suitableinsecticides in a water carrier for impregnation of wood for the firsttime.

Many of the known insecticide compounds presently available areobjectionable in varying degrees due to the toxicity they display towardanimal and plant life. This is in distinction to the antimicrobialcompounds of Section 1, which at use dilutions, are generally considerednon-toxic. Thus, when both toxicity and efficacy are important, it ispossible to use the antimicrobials in combination with knowninsecticides in order to substantially retain effectiveness whilereducing the amount of the toxic insecticides that must be used.

The examples which follow demonstrate the uses and practice of ourdiscoveries:

Example 1

The composition below was prepared and tested for protection of woodagainst termite attack (amounts are parts by weight):

Oxine 4.1

Copper hydrate 1.4

DDBSA 65.0

Methanol 29.5

The test procedure was AWPA (American Wood Preservers' Association)Methods M12-72, revised 1973. The termite species employed wasReticulitermes flavipes. The test blocks were southern pine sapwood andthe test period was four weeks.

    ______________________________________                                        Composition Retention in Wood (pcf)*                                                                  % Weight                                              Total Composition Cu-8-0    Loss                                              ______________________________________                                        0                 0         10.1                                              0.38              0.201     0.1                                               0.62              0.033     0.6                                               0.84              0.045     0                                                 ______________________________________                                    

These data indicate that the test composition provides adequateprotection against termites at the lowest concentration evaluated.

Example 2

The following composition was prepared (amounts are parts by weight).The composition was a true solution. When diluted 1:9 with water foruse, a true, stable solution resulted.

Oxine 7.4

Copper hydrate 2.5

DDBSA 53.0

Chlordane 10.0

Propylene glycol methyl ether 27.1

Example 3

The following compositions were prepared (amounts are parts by weight):

    ______________________________________                                                            A    B                                                    ______________________________________                                        Oxine                 7.4    7.8                                              Copper hydrate        2.5    2.7                                              DDBSA                 53.0   53.0                                             TBTO                  10.0   5.0                                              Propylene glycol methyl ether                                                                       27.1   31.5                                             ______________________________________                                    

Both formed true solutions are prepared. Diluted 1:9 with water,Composition A formed a stable colloidal emulsion. Diluted 1:9 and 1:99with water, Composition B formed true solutions.

Example 4

The following compositions were prepared (amounts are parts by weight):

    ______________________________________                                                            A    B                                                    ______________________________________                                        Oxine                 7.4    7.8                                              Copper hydrate        2.5    2.7                                              DDBSA                 53.0   53.0                                             Toxaphene             10.0   5.0                                              Propylene glycol methyl ether                                                                       27.1   31.5                                             ______________________________________                                    

Both produced true solutions as prepared. Composition A formed a stablecolloidal emulsion when diluted 1:9 with water. Composition B produced1:9 and 1:99 dilutions in water with a slightly hazy appearance,indicating a borderline condition between a true solution and acolloidal emulsion.

Example 5

The following composition was prepared (amounts are parts by weight):

Oxine 4.1

Copper hydrate 1.4

DDBSA 65.0

Malathion 5.0

Methanol 24.5

As prepared, the composition was a true solution. Dilution 1:99 withwater for use also produced a true solution.

Example 6

The following composition was made (amounts are parts by weight):

Oxine 4.1

Copper hydrate 1.4

DDBSA 65.0

Carbaryl 5.0

Methanol 24.5

The composition as prepared formed a true solution. When diluted 1:99with water, a true solution resulted.

Example 7

The following compositions were prepared (amounts are parts by weight):

    ______________________________________                                                         A    B                                                       ______________________________________                                        Oxine              4.1    4.1                                                 Copper hydrate     1.4    1.4                                                 DDBSA              65.0   65.0                                                Malathion          5.0    --                                                  Methyl parathion   --     5.0                                                 Methanol           24.5   24.5                                                ______________________________________                                    

Both compositions produced true solutions as prepared and when diluted1:100 with water.

Example 8

The following compositions, all dilutable for use with either water orpetroleum hydrocarbon solvents, and diluted in the range of 1:9 to 1:19,provide excellent marine and land service protection to wood whenimpregnated into the wood at a 20-25 pcf retention.

    ______________________________________                                        1         2      3      4    5    6    7    8                                 ______________________________________                                        Oxine    4    8      4.1   8.2  4.1  4.0 4.0   8.2  4                         Copper   3    7      1.4   2.8 --   --   --    2.8  1                         hydrate                                                                       DDBSA   60    60     60.0 60.0 60.0 60.0 60.0 60.0 60                         Stannous                                                                              --    --     --   --    7.0  4.5 4.5  --                              Sulfate                                                                       Chlordane                                                                             10    --     --   --   --   10.0 --   --                              Toxaphene                                                                             --    5      5.0  --   --   --   6.0  --                              TBTO    --    --     --   --   --   --   --   10.0 10                         Methanol                                                                              23    20     29.5 29.0 28.9 21.5 25.5 19.0 24                         ______________________________________                                    

Example 9

The following antifouling compositions (to reduce barnacle and othermarine organism encrustation of ship hulls), suitable as additives tomarine hull coatings, were prepared. The amounts listed are parts byweight:

    ______________________________________                                                   1         2      3                                                 ______________________________________                                        Oxine         9.0         9.0   15.0                                          Copper hydrate                                                                              7.0        --     10.0                                          Stannous sulfate                                                                           --           7.5   --                                            DDBSA        60.0        60.0   40.0                                          Methanol     24.0        23.5   35.0                                          ______________________________________                                    

These compositions can be incorporated in a number of marine coatingformulations in amounts up to 15%. Conventional antifouling components,such as cuprous oxide, may be used to augment the protection againstfouling organisms.

Example 10

The following compositions form true solutions in water as prepared, andtrue solutions when diluted 1:100 with water.

    ______________________________________                                                    A   B           C     D                                           ______________________________________                                        DDBSA         60    60          60  60                                        Chlordane      5    --          --  --                                        Toxaphene     --     5          --  --                                        Melathion     --    --           5  --                                        Methoxyclor   --    --          --   5                                        Methanol      35    35          35  35                                        ______________________________________                                    

In general terms, the diphenyl, carbamate and chlorinated cyclo organiccompound classes of insecticides function well in this invention. Anumber of insect control compounds in the organic phosphate classperform satisfactorily although stability time usually is reducedcompared to the preceding classes.

SECTION 5

We have also discovered that the compositions of Section 1 (comprisingsaid antimicrobial agent and said disubsituted aryl compound) are usefulfor protecting various manufactured goods and industrial commoditiesfrom microbial attack or degradation. The compositions disclosed inSection 1 exhibit broad spectrum antimicrobial efficacy againstmicroorganisms which degrade materials of economic value. The range ofactivity and high per unit efficiency covers all classes of fungi andboth Gram-positive and Gram-negative bacteria. Coupled with a number ofauxiliary properties which have few undesirable side effects duringapplication or in service, said compositions have unexpected and uniqueversatility for preservation of a wide range of materials and products.Heretofore available high-efficacy, broad-spectrum antimicrobial agentshave one or more of a wide range of undesirable properties that canseverely limit their utility. Among the frequently encounteredlimitations are mammalian toxicity, odor and color, skin and eyeirritation, volatility and instability, low persistence, and narrowantimicrobial spectrum. The compositions of Section 1 eliminate theseand other bars to usage.

The combination of properties of said compositions meet the specializedneeds of a broad and diverse range of material preservationapplications, including both finished products and in-processmanufacturing steps. Among the suitable uses providing one or moreunique results, the following may be given as representative:

Leather--The compositions of Section 1 have high substantivity toprotein substrates, low toxicity, low irritation to human and animaltissues, and high antimicrobial efficacy against the fungal, andespecially the bacterial, organisms that deteriorate leather.

Paints and adhesives--Water-based paints and adhesives require anantibacterial and antifungal agent for in-can preservation. Oil-basedpaints for exterior service frequently include antifungal agents. Thecompositions of Section 1 possess an unusual degree of appropriateantifungal and antibacterial action relative to persistence of actionafter application. Heretofore antibacterial action has been limited toin-can prevention of product deterioration and to exterior servicecontrol of fungi that aethetically disfigure paint and cause itsdeterioration.

Cutting oils and metal drawing compound--These water-based materialsrequire antifungal and antibacterial protection to prevent rancidity,slime development, and possible growth of organisms pathogenic to man.The compositions of Section 1 provide the needed broad spectrumantimicrobial activity with an unusual degree of safety to metalfabrication operating personnel.

Asphalt roofing--Both the asphalt and the cellulosic felt core inshingle and roll roofing are degraded by a variety of fungal species.The first major indication is product embrittlement which also is thestandard criterion of roofing failure. The compositions of Section 1have unique utility by reason of high substantivity, resistance to waterextraction, and heat resistance. Roofing is a severe long-term test ofthese properties.

Plastics--A substantial number of formulated polymers for a wide rangeof interior and exterior applications are subject to fungaldeterioration and aesthetic disfigurement, from bathroom shower curtainsto exterior building panels. The compositions of Section 1 offer unusualheat stability for these uses.

Textiles and fiber products--These products, including rope, netting,yarns, twine and carpeting, and particularly those made from naturalproducts such as cotton, hemp, linen and wool, generally are moresuceptible to biological breakdown than the synthetics although thelatter are not immune generally. Fungal deterioration is the mostcommon, except in the case of wool which is highly subject to bacterialdegradation. Protection from microorganism attack is difficult in severeservice conditions because of the very rapid rate of product failure.The compositions of Section 1 are uniquely suited for many suchpreservative uses because of high unit efficacy, low toxicity, low skinirritation, and resistance to actinic ray deactivation of antimicrobialefficacy.

Wood disinfection--Wood is employed in a number of applicationsinvolving direct (butcher blocks) and indirect (pallets) contact with abroad range of foodstuffs. The porosity of wood and other factors makesdisinfection, often a mandatory requirement, very difficult.Complicating this problem is the need for safety and low odor, taste andcolor in the antimicrobial composition. The compositions of Section 1uniquely fit these needs and, in addition, provides uniformity ofpenetration into the substrate.

Water flood oil recover--Bacteria introduced with water for secondaryoil field recovery may proliferate, clogging porous oil sands andinitiating corrosion of pipe and other equipment. The two most importantorganisms, Desulfovibrio desulfuricans and Thiobacillus suboxydans, arecontrolled with high efficacy by the compositions of Section 1 whichalso provide the ecological safety that is desirable in this use becauseof the enormous quantities of water involved.

Petroleum fuels--A number of fungal genera, including Hormodendrum, andbacterial genera, including Pseudomonas, Bacillus and Aerobacter, growabundantly at the water/oil interface of many petroleum fuels causingslime deformation and metallic corrosion. This may have especially graveconsequences in critical fuel uses such as for jet aircraft engines. Thehigh efficacy of the compositions of Section 1 plug long-termantimicrobial stability is of substantial value for fuel preservationuse.

Chemical toilets--The high efficacy of the compositions of Section 1plus low environmental contamination are of special value for suchdevices as planes, trains, boats, buses and compers, as well as instationary uses, for chemical toilets.

Logs--Logs for lumber and paper conversion frequently are stored underwater (water-sprayed piles or in ponds) for protection against fungaldegradation. While generally useful, this procedure has limited valuebecause high moisture content in the wood does not inhibit growth ofmany bacterial and certain soft-rot fungi, and because of theconsiderable difficulty, especially with water-sprayed piles of logs, inachieving all-over water/log contact. The compositions of Section 1 areuniquely useful for addition to the water because they have thenecessary high broad-spectrum efficacy and they are environmentallysafe.

Breweries--The brewing of beer is a microbiological process with highsusceptibility to ruinous results from even minor contamination withstray organisms of many types. The broad-spectrum, safe effectiveness ofthe compositions of Section 1 provide unique equipment protection, andthe persistence of antimicrobial activity is of great value in the dualarea of fungal and bacterial control on walls, ceilings and floors inthe vicinity of storage, processing and handling facilities.

SECTION 6

We have also discovered that the compositions of Section 1 are usefulfor the treatment of mammalian diseases.

The compositions of Section 1 are generally distinguished from theuseful antimicrobials known to the prior art in that they exhibit a highefficacy against a broad and non-selective range of numerous types ofmicroorganisms that are pathogenic to man and animals. Thesemicroorganisms include both Gram-positive and Gram-negative bacteria,the four primary classes of fungi (Ascomycets, Basidiomycetes,Phycomycetes and Fungi Imperfecti), yeasts envelope (lipoid) and naked(hydrophilic) viruses, protozoa and helminthes including mematoda andtrematoda. Broad spectrum antimicrobials that are safe for human andanimal use and have useful efficacy against Gram-positive andGram-negative bacteria and fungi are relatively rare and essentiallyunknown in the field of antimicrobials.

Broad spectrum antimicrobials are highly significant in overgrowthcontrol. Since various types of microorganisms compete with each otherfor survival, both inside and outside the mammilian body, many widelyemployed narrow-spectrum antimicrobials which control only selectedorganisms, provide an environment for the growth of other organisms.This is of notable concern to the medical profession in the widespreadconsumer use of medicated soaps and other preparations for the topicalapplication in which, as a rule, the antimicrobial agents used in thepreparations have practical effectiveness essentially only againstGram-positive bacteria. This can and does allow establishment andproliferation of Gram-negative bacterial and fungal pathogens notusually present on the skin, which organisms can be considerably moredangerous to the host than Gram-positive bacterial that are broughtunder control. By way of specific example, many of the commonpreparations will, with continued use, encourage the growth of theGram-negative Pseudomonas sp., which is difficult to control even withantibiotics.

Many known antimicrobials for use in treating mammilian disease are alsodeficient in that they have relatively high toxicity and may have suchhigh irritability to animal tissue as to render them practically oflittle use. These problems, particularly that of toxicity, are assumingparticular importance in more recent times as various health andgovernmental agencies place increasingly stringent requirements onantimicrobials before permitting their use.

It has been found that the compositions of Section 1 are efficaciousagainst a broad and non-selective range of microorganisms that causemammilary disease, and are relatively nontoxic to mammals and have lowirritation to mammal tissue. The compositions of Section 1 arerelatively low in color, odor and taste; have long stability undernormal ambient conditions; have low volatility; are heat and lightstable; can be diluted for use in many carriers; become insoluable andsubstantive to a host upon application; and are effective cleaning andwetting agents.

While it is believed necessary in the practice of this invention to forman initial solution of the antimicrobial agent with the disubstitutedaryl compound (as these are defined in Section 1) the antimicrobialagent may, when diluted for use, begin to form a very fine precipitate.This precipitation from solution may and usually will become completeafter the composition has been applied to a substrate.

The compositions of Section 1 eliminate overgrowth by reason ofbroad-spectrum control of all major types of microbiological flora. Thisrange of activity is both microbiostatic and microbiocidal, in contrastto many present products which are effective primarily as biostats. Theactivity is both initial and residual, exhibiting both rapid initialorganism kill or inhibition, depending upon the concentration of activeingredients employed, and considerable residual persistence ofantimicrobial effectiveness.

The compositions of Section 1 combine a number of auxiliary propertiesthat not only are prerequisites for human and animal use, but which, intotal, are unique in the field of antimicrobials. These include:

Low mammalian toxicity. The compositions of Section 1 have much lowertoxicity than the majority of anticicrobials in use today and have beengiven laboratory ratings of "not toxic orally."

Low skin and eye irritation. The range of skin and eye irritation isfrom low for concentrates to low to zero in dilute concentrationseffective for use. Opthalmic preparations containing the compositions ofSection 1 for antimicrobial eye medication exhibit no eye irritation.

Low color, odor and taste. Concentrates of the compositions of Section 1exhibit a low inherent odor level, and impart minor to no color to mostsubstrates. At suitable use dilutions, such compositions impart nocolor, no odor, and very low to zero taste. It therefore is generallypractical in formulated products containing the compositions of Section1 to incorporate colorants, fragrances or masking agents, and tasteflavoring agents as may be desired.

Shelf stability. No significant changes take place in antimicrobialproperties in the compositions of Section 1 even after long storageperiods under normal ambient conditions.

Low volatility. Use dilutions of the compositions of Section 1 maintaininitial efficacy upon standing in open containers for long time periods.Evaporation of carriers, usually water, will increase efficacy byraising the ratio of composition to carrier in the use dilution. Anumber of presently used antimicrobials require special use precautionsbecause of volatility or sublimation processes.

High air, heat and light stability. In contrast to a number of presentproducts, the compositions of Section 1 exhibit no deterioration or lossof efficacy from prolonged exposure to air or light. Heat stability upto an estimated 300° F. allows a range of use conditions not feasiblewith many currently available antimicrobials. Heat plus inherentantimicrobial action of the compositions provide a flexibility of useand performance unmatched by any narrow-spectrum antimicrobials. Thisincreased flexibility is particularly useful in that no specialequipment is needed for utilization to offset volatility, light or airinstability, active ingredient sublimation or the like.

Carrier versatility. While water is the most widely used and versatileuse diluent for antimicrobials, the compositions of Section 1 may becarried in a very broad range of polar (including water) and non-polarsolvents, and combinations thereof. Carriers other than water may bevery useful in a variety of end uses for a number of reasons includingenhanced antimicrobial action, need for rapid carrier evaporation,general unsuitability of water, need for low or non-volatility of thecarrier, the desire for carrier lubricity or emolliency, the adverseeffect of water upon the host organism or substrate and the like.Suitable carriers include a broad range of hydrocarbons, alcohols,ketones, ethers, glycols, chlorinated organic solvents, esters, acetyls,phtalates, adipates, aldehydes, anhydrides, acids, silicone fluids,nitroparaffins plus a variety of the more exotic solvents such asN-vinyl-2-pyrrolindone, dimethyl sulfoxide and dimethyl formamide. Thiscarrier versatility is in sharp contrast with most antimicrobials whichare either imcompatible with, or are insoluble in, many types ofcarriers.

Insolubility after application. For general use, the preferredembodiment of compositions of Section 1 are soluble in the use-dilutioncarriers. Such ready-for-use compositions, notably in a water carrier,become water-insoluble after application to the host. This is in sharpcontrast to most antimicrobials which retain water solubility afterapplication. This feature offers obvious residual persistence advantagessince removal by aqueous media is a major means by which initialeffectiveness of antimicrobial agents is rapidly diminished.

Substantivity. The compositions of Section 1 not only turn waterinsoluble rapidly after application as just mentioned, but also exhibitstrikingly high affinity for a number of surfaces, most notablycellulosic and proteinaceous substrates. This is true under usualparameters of use. It normally occurs near-instantly and in the wetcondition. The result for a number of uses is unusually high retentionof antimicrobial action yielding surprisingly long efficacy life.

Wetting-cleaning action. The compositions of Section 1 possess strong,inherent wetting and detergent activity. This feature is a significantaid in penetrating crevices and areas of difficult access. Further, thehigh detergent-cleaning action is an important adjunct for many medicalantisepsis and disinfection applications.

Efficaceous in the presence of organic matter. Unlike many antimicrobialcompositions such as a number of the quaternary amines, the efficacy ofthe compositions of Section 1 are not destroyed by the presence oforganic material.

The following is an incomplete, but representative listing of uses forthe compositions of Section 1 which uses are unique in kind or degree ofeffectiveness. A feature common to these uses is effective control of anuncommonly large number of the major classes of pahogens as previouslydescribed. This feature has primary importance where kill orinactivation is mandatory and in uses where non-selective control of allorganisms is desirable to prevent overgrowth of pathogenic floraotherwise not controlled by selective-spectrum antimicrobials. Suchovergrowth can be both rapid and dangerous.

Surgical antiseptics. The compositions of Section 1 provide extremelyhigh skin degerming capacity as measured by reduction in the transientand resident flora count as shown in Example. It is believed that, inaddition to the demonstrated high antimicrobial efficacy, thecompositions of Section 1 may have exceptional capacity to act upon thedifficult to reach flora under the outer, cutaneous layer of skin whichconsists of the flat plaques of keratin. In view of the generally heldbelief that total degerming is not possible short of destruction of theskin itself, the greater the reduction of flora, the lower the risk ofthe patient from a surgeon who is compelled to operate with hands thatcannot be fully disinfected and to make incisions through skin thatcannot be made entirely germ-free. The exceptional flora count reductionafforded on the skin by the compositions of Section 1 is unexpected inview of the long known difficulty of the skin degerming and theacknowledged fact that, as the count reduction approaches thetheoretical 100% maximum, the problems of achieving even a very smallincremental improvement in the count becomes progressively moredifficult by orders of magnitude.

Another reason for desiring to achieve the highest reduction in skincount that is feasible, both on the surgical team and the patient, isthe fact that surgical gowns, gloves, patient draping, folds in theskin, the perineal and umbilicus areas and the like provide bothprotectin and favorable (warm and moist) conditions for rapid andaccelerated growth of the remaining organisms. Hence the high order ofinitial flora reduction, and the substantivity and persistence ofantimicrobial activity of the compositions, has important utility whenconsideration is given to the fact that containment of the rapidregrowth generally is very difficult. For instance, perforation ofgloves worn by the surgical team is a frequent occurrence with numbersas high as 70% being reported. With glove punctures or tears, floraladened sweat and the like may leak large numbers of microorganisms intoa surgical wound.

The ultimate in degerming effectiveness of the composition is obtainedby means of an after-application of the composition following thesurgical scrub or patient preoperative skin preparation. This may be arinse in a water solution of the composition, or an alcoholic tincture,or most effective of all, an ointment carefully rubbed into the skin,under the fingernails and into protective folds of the skin and mucousmembranes. For the hands of operating personnel, an ointment whichleaves the hands non-slippery can be readily formulated. Not only doessuch an ointment or cream present physical barrier of sorts to themovement of microflora, but much more importantly, a finite layer of thehighly toxic composition is interposed between the organisms remainingafter the degerming step and the surgical wound or any other area of thepatient and surgical personnel subject to pathogenic contamination.

Where desired, the compounds clean as well as disinfect. The cleaningaction can be applied to unbroken skin, wounds and body cavaties.

Disinfection of medical and surgical materials. The compositions ofSection 1 are suitable for disinfection of critical items, such asscalpel blades, transfer forceps and cardiac catheters; semi-criticalitems such as thermometers, aspirator tubes and cystoscopes; andnon-critical items such as face masks, rebreathing bags and a variety ofaccessory items.

The broad antimicrobial spectrum of the compositions coupled with readyadaptability to the use of heat, and compatibility with water carriersand mixtures with higher solvents such as propylene glycol, providesunique high level disinfection of critical items. Items of lessercriticality are disinfected rapidly in the cold.

Dental antisepsis and disinfection. Hot and cold disinfection andsterilization of instruments and a broad range of other items ispractical with the compositions of Section 1. For scrub-up of oralsurgery personnel the just preceding procedures are highly effective.The compositions of Section 1 exhibit particularly useful efficacy forthe frequent daily hand washings required of dental personnel betweenpatients and for routine procedures.

The oral cavity harbors large microbial polulations which are mostdifficult to control. Limited and general oral antisepsis, particularlyfor prevention of post-treatment infections, is effectively accomplishedwith the compositions of Section 1.

Disease control. The broad spectrum antimicrobial activity of thecompositions of Section 1 make these uniquely suitable for a wide rangeof pathogenic conditions including mastitis in lactating females,bacterial and fungal hemorrhoidal conditions; ringworm; vulvovaginalcandidiasis; athlete's foot; oral moniliasis; mycotic skin infectionswith casual agents that include Candida albican, Trichophyton sp.,Epidermaphyton floccosum, Microsporum canis and Microsporum audouini;Trichomonal and non-specific vaginitis, urinary infections; hair andscalp conditions; a variety of nemotodal and tremotodal conditions.

Contraception. The compositions of this invention are spermicidal.

Specialty water disinfection. The compositions of Section 1 find utilityin therapeutic baths and various water soaking treatments.

Environmental control of fungal allergies. A substantial portion ofhuman allergic conditions is caused by a wide range of molds and mildewswhich infest homes, living quarters and other habitated buildings. Suchallergies can be alleviated by control of the fungal organisms. To beeffective, antifungal application must be made to all surfaces andarticles including walls, floors, ceilings, crawl spaces and basements,furniture, drapes and carpets, mattresses and pillows.

The compositions of Section 1 have the necessary prerequisites for suchapplication, e.g., no color or odor, low taste, and no damage to orunacceptable residue on treated surfaces: These requirements arecombined with extermely high fungistatic and fungicidal efficacy. Suchantifungal treatment can be coupled in a number of cases with cleaning,leaving a substantive and persistent residue on carpets, upholstery,walls, floors, tiles and other surfaces.

Pharmaceutical, toiletry and cosmetic product preservation. Thecompositions of Section 1 possess near-ideal properties for these uses,including very high microbiological activity against the representativeorganisms that cause product deterioration and disease to the user suchas Staphylococcus aureus, Escherichia coli, Candida albicans,Pseudomonas aeruginosa and Aspergillis niger spores. Control of thelatter generally is difficult to achieve. Control of Ps. aeruginosa alsois difficult and of considerable importance because this organism causespathogenic conditions in man and animals, against which antibotictreatment is relatively ineffective. Control of Pseudomonas isparticularly important in critical products such as opthalmicpreparations. Ps. aeruginosa, which few antimicrobials control reliably,is considered by some authorities to be the most troublesome as well asthe most ubiquitious.

Skin odor control. The compositions of Section 1 offer uniqueperformance in this area. Skin odor, bacterial in origin, generally iscaused by resident Gram-positive skin flora picked up in sweatcontaining nutrients for rapid bacterial growth. Presently availableantimicrobials in underarm and foot deodorants, medicated soaps and thelike, are relatively effective against these offensive odor-producingorganisms, but generally are ineffective against a variety of otherorganisms that, while not necessarily causing disagreeable odor, aredangerous to man, especially if given the earlier described opportunityto proliferate in the relative absence of Gram-positive bacteria. Thisis especially true of the Gram-negative Pseudomonas and to a lesserextent Candida albicans. Present antimicrobials capable of overall broadspectrum control are not suitable for wide consumer use for a number ofreasons including toxicity, odor, color, skin sensivity or irritation.Indeed many have been banned by governmental agencies except forperscription use.

The compositions of Section 1 have a prerequisite safety and otherfeatures needed for broad consumer usage. These compositions uniquelyprovide a balance of antimicrobial activity that prevents overgrowth ofuncontrolled organisms. Entirely unexpectedly, perhaps due to theirsubstantive nature, the compositions exhibit skin odor control for muchlonger periods than present products.

Even more unexpected is the long term odor protection provided byresidual action only. When the formulated compositions are applied withwater, and dried, no odor will develop for much longer periods thanpresent underarm deoderants allow.

Medicated, deoderant soaps are in wide use for bathing. Used regularly,these provide a significant degree of body odor control, although themagnitude of control is considerably less than that afforded by underarmdeodorants. Further the more effective medicants, such ashexachlorophene, have been banned for general use. Bathing withformulated compositions of Section 1 provide cleaning power equal to thebest of current products and, quite remarkably, provide sole control ofbody and skin odor for much longer periods of time than presentmedicated soaps for underarm and foot deodorant preparations, medicatedvaginal douches, and medicated hair shampoos.

It would appear that the after-applicaton water insolubility of thecompositions and high sutstantivity to skin has a significant role inthe demonstrated long term odor control. The insolubility/substantivityfactor is much greater than might be expected in view of the extremeseverity of the service conditions.

General bathing with formulated compositions of the invention alsoprovides control of the ubiquitious conditions known as athlete's foot,jock itch, vaginitis and other assorted skin and mucuous membraneconditions.

Our discoveries are illustrated by the following compositions:

Example 1

The following composition was prepared and tested for skinsubstantivity:

Oxine 4.1 parts by weight

Copper hydrate 1.4 parts by weight

DDBSA 65.0 parts by weight

Propylene glycol 29.5 parts by weight

Ten parts by weight of this composition was blended (heated at 140° F.with constant agitation) with:

Oleyl alcohol ethoxylate (20 EO) 15 parts by weight

Lauryl alcohol ethoxylate (25 EO) 25 parts by weight

Octyl phenol ethoxylate (9 EO) 5 parts by weight

Acetylated lanolin 2 parts by weight

Distilled water 43 parts by weight

The resulting formulation was a transparent pale yellow-green, mediumviscosity liquid. One gram was used to wash the hands. After waterrinsing and drying the hands, a drop of 1% dithio oxamide copperindicator was applied to various parts of the hands. Immediatedevelopment of a black color indicated presence of copper (in Cu-8-Q) onthe skin. Using Ivory soap, the hands were washed, rinsed and driedtwice more. The black color remained, requiring several days todisappear.

This formulation was an effective hand cleaner, exhibited no skinirritation and left the skin with a residual soft, smooth feel. Used forbathing and as a hair shampoo, the formulation exhibited the sameresults.

Example 2

The final formulation of the preceding Example was used to wash theentire body, including the scalp and hair. No skin odor developed untilthe middle of the fourth day. Commercially available underarm deodorants(two brands) previously tested by three subjects, following a bath witha commonly used medicated bar soap, failed to stop odor development foreven 24 hours.

Example 3

The following composition was prepared and evaluated for underarm odorcontrol:

Oxine 2.05 parts by weight

Copper gydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Propylene glycol 57.25 parts by weight

Three parts of this composition was blended as before with:

Prophlene glycol 5 parts by weight

Glycerin 5 parts by weight

Ethanol 5 parts by weight

Water 82 parts by weight

Four test subjects applied this final formulation under one arm and abrand name underarm deodorant under the other arm. Total odor controlranged from a minimum of 31/2 days to almost 6 days for the testsubjects whereas none of the three brand name comparative controldeodorants provided complete odor control for a full 24 hours.

Essentially the same odor control results were obtained using thefollowing formulation in ointment form:

Two parts of the foregoing composition were blended with:

Oleyl alcohol ethoxylate (20 EO) 18

Lauryl alcohol ethoxylate (25 mol) 9

Acetylated lanolin 1

Glycerin 9

Propylene glycol 4

Polyvinyl pyrrolidone, 60% in water 1

Distilled water 56

No underarm irritation was noted by any test subject, although one testsubject had a history of irritation problems with a number of brand nameproducts.

Example 4

The second formulation in the preceding Example was applied once dailyby eight test subjects to the skin between the toes for control of"Athlete's Foot". The condition was brought largely under control anddefinite signs of skin healing were exhibited in all cases by the end of24 hours. Two of the cases had previously resisted control with severalover-the-counter brand name antifungals. One of the two, a virulentinfection, had reached the bleeding stage from deeply cracked skin and abacterial infection started, despite twice daily application for eightdays of a 1% solution of Toluaftate which has gained broad recognitionfor effective control of "Athlete's Foot". The Toluaftate product notonly failed to control the case of "Athlete's Foot" but also the ensuingbacterial infection. The test formulation brought both the fungal andbacterial infections under control in 24 hours.

The causal organisms of this last fungal infection almost certainly werenot those defined medically as causing "Athlete's Foot", but rather oneor more other fungi which to the layman (but not a dermatologist)produces similar or identical symptoms and hence is called "Athlete'sFoot". The Tolunaftate failed in that its narrow-spectrum antifungalactivity had no effect upon the causal organisms in the test case andbecause it has no significant antibacterial efficacy. Very few"Athlete's Foot" preparations provide even a low order of antibacterialactivity.

The compositions of the invention, therefore, offer not only potentcontrol of true "Athlete's Foot" but also of a wide range of fungal andsometimes resulting bacterial conditions which to the public is"Athlete's Foot". The importance of the major improvement over existingtechnology is the fact that in the vast majority of cases the public,not a dermatologist, makes the diagnosis and determines the treatment.

Example 5

Hemorrhoids, varicose veins of the rectum, are suffered by an estimated40% to 50% of the adult population. Prescriptions and over-the-counterpreparations, ointments and suppositories, are in wide, almost universaluse for alleviation of these widespread symptoms of hemorrhoids: (1)bleeding from the rectum, (2) bacterial infection which can causeinflammation of tissues and pain and (3) fungal infection (caused byorganisms related to "Athlete's Foot" and ringworm causal agents) whichbrings about itching which at times can be near-intolerable.

Present state-of-the-art hemorrhoidal preparations contain anantimicrobial in a soothing, emollient ointment base; some also containa topical anesthetic for pain control. The antimicrobial is designed toserve a dual purpose: (a) to allow healing, thereby controlling rectalbleeding, bacterial infection and pain and (b) to control itching. Theseobjectives are difficult ones to achieve because of presentunavailability of sufficiently potent yet safe antimicrobials, andbecause of the great difficulty of obtaining effective antimicrobialaction in the inevitable presence of large amounts of organic matter.

The first formulation of the preceding Example was applied forhemorrhoid symptom control. Rapid and more effective relief of symptomsresulted, as compared to commercially available products. In oneinstance involving almost daily rectal bleeding for over six yearsdespite daily use of a brand name product, the test formulation broughtabout complete cessation of bleeding within 24 hours for almost threemonths with no further application of the test formulation. At firstresumption of bleeding, application of the test formulation againcontrolled all bleeding and weekly and bi-weekly application thereafterfor the next six months prevented all further bleeding.

The broad-spectrum efficacy of the compositions of the invention asdemonstrated by the in-vivo and in-vitro data herein, and in mycopending application referred to above, provide results of a magnitudenot heretofore available for treatment of pathogenic conditions of manand animals, and for health related applications. The idealantimicrobial is highly and rapidly toxic to the target organisms andnon-toxic to the host organisms and possesses to a high degree thedesirable prerequisites of low taste, odor, high stability and the like.The compositions of the invention come closer to the theoretical idealthan anything heretofore known by a margin ranging from significantlybetter to almost infinitely superior.

Example 6

The following composition was tested for minimum fungicidalconcentration and compared to two well known antifungalchemicals--pentachlorophenol and 2,3,5trichloro-4-propyl-sulfonylpyridine--and DDBSA.

Oxine 8.2 parts by weight

Copper hydrate 2.8 parts by weight

DDBSA 59.0 parts by weight

Propylene glycol methyl ether 30.0 parts by weight

All of the test composition concentrations to be tested wereincorporated in the fungal growth media (agar) in accordance withstandard microbiological practices. Agar plugs containing the testfungicides then were inoculated with a sporulating culture andinoculated at the temperatures and times specified by The American TypeCulture Collection (ATCC) recommendations. The plugs were then scoredfor absence or presence or organism growth. The results are shown in thefollowing table. Minimum fungicidal concentrations were determinedagainst a broad spectrum of fungi that are detrimental to man,foodstuffs and materials and which can result in metabolite formations(mycotoxins) of extreme toxicity to man and animals.

In the table below, Composition A is that of this Example 25 and theactive ingredient is Cu-8-Q; Composition B is DDBSA; Composition C ispentachlorophenol; and Composition D is 2,3,5-trichloro-4-propylsulfonylpyridine. Where no concentration is listed, no data is available. Thestated value of "1" means 1 or fewer ppm.

    ______________________________________                                                     Minimum Fungicidal Concentration                                              (ppm of active ingredient)                                                    A     B         C       D                                        ______________________________________                                        Aspergillis niger                                                                            1       10,000    1-3   --                                     (ATCC 9642)                                                                   Aspergillis terreus                                                                          1       100       --    36                                     (ATCC 10609)                                                                  Aspergillis flavus                                                                           1       1,000     22-54 --                                     (ATCC 11655)                                                                  Alternaria alternata                                                                         1       --        --    --                                     (ATCC 13963)                                                                  Aureobasidium pullulans                                                                      1       100       --    --                                     (ATCC 16624)                                                                  Lenzites trabea                                                                              1       100       1-3   --                                     (ATCC 11539)                                                                  Polyporus tulipiferae                                                                        1       100       1-3   --                                     (ATCC 11245)                                                                  Penicillium brevi                                                                            1       100       --    --                                     compactum (ATCC 16024)                                                        Rhizopus stolonifer                                                                          1       100       1-3   --                                     (ATCC 24794)                                                                  Trichoderma viride                                                                           10      100       --    --                                     (ATCC 8678)                                                                   Trichoderma sp.                                                                              1       100       --    --                                     (ATCC 12668)                                                                  Candida albicans                                                                             1       1,000     --     3                                     (ATCC 10259)                                                                  ______________________________________                                    

These results illustrate the high efficacy of the composition of thisinvention and confirm the fact that an antifungal composition preparedfrom a Cu-8-Q/DDBSA solution is much superior to DDBSA alone. Theresults also indicate the favorable relative efficacy of the testcomposition compared to the two commercially available fungicides ofrecognized high performance.

Example 7

Using the standard AOAC fungicidal test method (12th Edition, 1975), thecomposition below was evaluated against two widespread fungi.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Isopropanol 32.00 parts by weight

Demineralized water 25.33 parts by weight

The two fungi were Aspergillis niger, a ubiquitous black fungus whichflourishes on a broad range of substrates, and Trichophytonmentagrophytes, a cause of "athlete's foot."

A. niger--at 1:200 use dilution in a water carrier, no growth after 10minutes' exposure.

T. mentagrophytes--at 1:750 use dilution in a water carrier, no growthafter 10 minutes' exposure.

Simular but somewhat lower efficacy results were obtained bysubstituting zinc-8-Q or aluminum-8-Q in the composition of thisexample, produced by reacting zinc oxide and aluminum hydroxiderespectively with oxine.

Example 8

The DDBSA/Cu-8-Q solution of Example 7 diluted 1:400 in a water carrier,was applied by spray nine times, at two-week intervals, to peach andnectarine cultivars during the growing season. The results against brownrot (Monolinia fructocola), compared to nontreated trees, is presentedbelow.

    ______________________________________                                                         % Fruit Affected                                                              Peach Nectarine                                              ______________________________________                                        At harvest (treated)                                                                              1       3                                                 At harvest (untreated)                                                                           15      43                                                 Five days later (treated)                                                                         3       6                                                 Five days later (untreated)                                                                      60      67                                                 ______________________________________                                    

Example 9

The DDBSA/Cu-8-Q solution of Example 7 was tested in vitro against amajor turf pathogen, Helminthosporium vagans, via a standard agar plateculture technique, with these results:

    ______________________________________                                                          Fungus Colony Diameter                                      ______________________________________                                        1:6700 use dilution in water carrier                                                              1         mm                                              1:3350 use dilution in water carrier                                                              0                                                         Control             21        mm                                              ______________________________________                                    

The results demonstrate very high efficacy in controlling this importantpathogen. Complete control of H. vagans was achieved in this assaybetween 3.7 and 7.5 ppm of Cu-8-Q.

As illustrated in the examples to follow, the compositions of thisinvention have high efficacy against a broad spectrum of bacteria thatare pathogenic to mammals and plant life, that contribute to reducedwater quality, that cause deterioration of foodstuffs, that degrade abroad range of manufactured and natural materials and products, andwhich generate toxic metabolites (bacteria-toxins) that are among themost poisonous substances known to man.

Of particular interest in high efficiency against Gram-negative as wellas Gram-positive microorganisms. Few antibacterial materials nowavailable are effective against the Gram-negatives and still fewerprovide economical control of them. A number of available antibacterialstoxic to Gram-negative organisms have practical limitations whichseverely restrict use, including high mammalian toxicity, phytotoxicity,corrosiveness to skin and a variety of materials, strong odor, strongcolor, high volatility, low or erratic shelf stability, low ornonexistent residual activity, and prohibition of use at elevatedtemperatures.

The basic significance in the need for Gram-negative control lies in thefact that this bacterial category includes a number of widespread,virulent pathogens which are difficult to impossible to control withpresent available antibiotics, notably Pseudomonas sp. typified byPseudomonas aeruginosa PRD-10, the standard strain in the United Statesfor evaluation of antibacterials for mandatory Gram-negative controlapplications.

The compositions herein disclosed eliminate or substantially reducethese use limitations inherent in many other germicides. Thecompositions are quite unique in having strong Gram-positive andGram-negative activity combined with broad versatility of formulationand use plus a high degree of safety (low toxicity and zero to low skinand eye irritation). Add to this the high efficacy, broad spectrumantifungal activity of the compositions of this invention and theresulting range of toxicity to target organisms and safety to man, themost sensitive of hosts, is unique indeed.

The balance of toxicity provided by this invention to Gram-positive,Gram-negative and fungal microorganisms has special value in the broadconsumer field of skin deodorancy. Present antibacterials suffer fromthe fact that they are effective primarily against Gram-positives,allowing Gram-negative and fungi overgrowth, a condition considereddangerous by many authorities.

Example 10

The DDBSA/Cu-8-Q solution of Example 6 was tested, along with a numberof well known antimicrobial agents, against a broad spectrum screen ofeconomically important Gram-positive and Gram-negative bacteria. Allantimicrobial agents were incorporated in the agar bacterial growthmedia according to standard microbiological practices. The bacterialspecies were grown in nutrient broth; 24-hour cultures, the inoculum,then were streaked onto the nutrient agar plates containing the testantimicrobials. After a 24-hour incubation at the appropriatetemperature, the plates were rated for presence or absence of bacterialgrowth.

Minimum bactericidal concentrations for each of the tested agents arestated in the following tabulation of results in parts per million (ppm)of active ingredient as defined in the description of each agent.

    __________________________________________________________________________                    Antimicrobial Agent                                                           (ppm* of active ingredient)                                   Bacteria (ATCC No.)                                                                           A   B    C  D  E   F     G                                    __________________________________________________________________________    Gram-positive:                                                                Bacillus cereus 1   100  --  7 8    5-10 --                                   Bacillus lichenforms (27326)                                                                  1   100  --  7 8   2-5   --                                   Bacillus megaterium (27327)                                                                   1   100  --  7 8   --    --                                   Bacillus subtilis (37328)                                                                     1   100  -- 750                                                                              8   --     3                                   Micrococcus flavus (10240)                                                                    1   100  --  7 8   --    --                                   Mycobacterium phlei (15610)                                                                   1    10  --  7 8   --     3                                   Staphylococcus aureus (6538)                                                                  1   100  2083                                                                              7 8   1-3    3                                   Gram-negative:                                                                Alcaligenes faecalis (337)                                                                    10  1000 -- 750                                                                              80  --    --                                   Alcaligenes marshalii (21030)                                                                 104 100  --  7 8   --    --                                   Esherichia coli (11229)                                                                       104 10,000                                                                             -- 750                                                                              80  250-500                                                                             165                                  Flavobacterium arboresceus (4358)                                                             10  10   4166                                                                              7 8   --    --                                   Klebsiella pneumoniae (4356)                                                                  10  10,000                                                                             -- 750                                                                              8   --    --                                   Proteus vulgaris                                                                              10  1000 -- 750                                                                              800 --    --                                   Pseudomonas aeruginosa (15442)                                                                104 1000 4166                                                                             750                                                                              800 1000-2500                                                                           165                                  Salmonella cholerasuis (10708)                                                                104 1000 -- 750                                                                              80  250-500                                                                             165                                  Salmonella typhi (6539)                                                                       104 1000 2083                                                                             750                                                                              80  --    165                                  __________________________________________________________________________     *stated value of "1" means 1 or less                                          A = the DDBSA/Cu8-Q solution of Example 6 with the active ingredient          expressed in terms of Cu8-Q.                                                  B = DDBSA.                                                                    C = phenol                                                                    D = Betadine, an iodine/polyvinylpyrrolidone complex containing 0.75%         iodine. The active ingredient is iodine.                                      E = Alkyl dimethyl ammonium chlorides (61% C.sub.12, 23% C.sub.14, 11%        C.sub.16 and 3% C.sub.10).                                                    F = sodium pentachlorophenate                                                 G = 2,3,5trichloro-4-propylsulfonyl pyridine.                            

These data demonstrate the high efficacy of the composition of Example6. On the basis of the average of the efficacies against all the testorganisms, Composition A is 45 times superior to Composition B; 88 timesbetter than Composition C; 10.7 times better than Composition D; and 3.5times superior to Composition E.

On the basis of the average of the efficacies against the three testbacteria (Staphylococcus aureus, Salmonella cholerasuis and Pseudomonasaeruginosa PRD-10) required by the Environmental Protection Agency of a"hospital grade" disinfectant, Composition A is 10 times better thanComposition B; 7.2 times better than Composition D; and 1.6 times betterthan Composition E.

Example 10A

The composition set forth below was prepared by previously describedprocedures:

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

Iospropanol 32.00 parts by weight

DDBSA 40.00 parts by weight

Water (demineralized) 25.22 parts by weight

When evaluated as a bactericide by the AOAC Use Dilution Method (12thEdition, 1975), 10 ring carriers per organism, the following resultswere obtained (A=subculture and B=resubculture):

    ______________________________________                                                    Use Dilution in                                                                         Negative  Positive                                                  Water Carrier                                                                           A      B      A    B                                    ______________________________________                                        Staphylococcus aureus                                                                       1:1000      10     10   0    0                                  Salmonella cholerasuis                                                                      1:1000      10     10   0    0                                  (PRD-10)                                                                      Pseudomonas aeruginosa                                                                      1:400       10     10   0    0                                  Aerobacter aerogenes                                                                        1:400       10     10   0    0                                  ______________________________________                                    

A ten-minute kill is required against the first three pathogens for saleas a hospital grade disinfectant. Efficacy against the fourth organism,a major cause of slime to recirculated cooling water systems and pulpand paper mills, demonstrates utility of the composition as a slimicide.

Example 11

This composition was prepared and tested at one use dilution, 1:50 inwater carrier, against the causal agent of potato ring rot bacteria(Corynebacterium sepedonicum):

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

Infected potato seed readily contaminate potato seed cutters, sacks,bins, cellars, trucks and planting equipment with the highly infectiousring rot bacteria. The result may be infected potato plants, tubers andreduced yields.

The test procedure consisted of dipping unpainted, planed wood laths(6") into a slurry of infected ring rot tuber tissue, allowing excessslurry to drain off (3-5 minutes) and then spraying the contaminatedlath with the test antibacterials. Three to five minutes later, healthyNorgold Russet potato seed pieces were rubbed vigorously against bothsides of the contaminated and antibacterial-treated laths. The processwas repeated using laths not contaminated with C. sepedonicum buttreated with the test antibacterial agent. The rubbed seed pieces werestored in bags and later planted at the appropriate time.

In addition to the composition of the invention, untreated controls, 20%Clorox (1.05% sodium hypochlorite in water), formaldehyde (37% formalindiluted 1:120 in water) and Roccal (benzalkonium chloride or zephiranchloride) diluted with water to 800 ppm concentration were tested. Theresults of the test are tabulated below and refer to plants and tubersproduced from the tubbed test seed pieces.

    __________________________________________________________________________    Antimicrobial                                                                          Ring Rot Contaminated                                                                     % Plant Stored                                                                        % Ring Rot Plants                                                                       % Ring Rot Tubers                                                                       Yield cwt/acre               __________________________________________________________________________    None (control)                                                                         Yes         98      23        8         493                          None (control)                                                                         No          95      0         0         609                          DDBSA/Cu-8-Q                                                                           Yes         98      0         2         631                          DDBSA/Cu-8-Q                                                                           No          100     0         0         602                          20% Clorox                                                                             Yes         98      20        9         500                          20% Clorox                                                                             No          98      0         0         602                          Roccal   Yes         98      20        9         515                          Roccal   No          98      0         0         638                          __________________________________________________________________________

The composition of this example demonstrates superior control of thering rot bacterium. Other species of the genus Corynebacterium arecausal agents of disease in man and a variety of plant life.

Example 12

The composition below was prepared and tested for speed and range ofantibacterial activity, in the absence and presence of organic matter(blood) for use in hospital disinfection, cold sterilization andantisepsis.

Oxine 4.1 parts by weight

Copper hydrate 1.4 parts by weight

DDBSA 65.0 parts by weight

Propylene glycol methyl ether 29.5 parts by weight

Many antimicrobial agents are partially or totally deactivated in thepresence of organic matter, constituting a severe limitation toeffectiveness of such agents for a number of uses such as woundantisepsis and medical instrumentation and surface disinfection wherelarge amounts of organic matter often are encountered and sometimes areunavoidable.

The AOAC Use Dilution Confirmation Test (12th Edition, 1970) wasmodified as follows:

(a) The test temperature was 37° C.

(b) The ring carriers were soaked in sheep blood for two hours,air-dried for one hour, then contaminated with the test pathogen.

(c) The contaminated rings were contacted with the test antibacterialagent for 30-second, one-minute and three-minute periods.

The results are set forth in the following table, in which:

0=no growth in 10 of 10 tubes tested

1=growth in 1 of 10 tubes tested

2=growth in 2 of 10 tubes tested

3=growth in 3 of 10 tubes tested etc.

    __________________________________________________________________________                Use Dilution in                                                                       In Absence of Blood                                                                       In Presence of Blood                          Test Pathogen                                                                             Water Carrier                                                                         30 sec.                                                                           1 min.                                                                            3 min.                                                                            30 sec.                                                                           1 min.                                                                            3 min.                                __________________________________________________________________________    Staphylococcus aureus                                                                     Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 6538) 1:10    0   0   0   0   0   0                                                  1:100  0   0   0   3   6   3                                     Salmonella typhi                                                                          Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 6539) 1:10    0   0   0   0   0   0                                                 1:00    0   0   0   0   0   0                                     Pseudomonas aeruginosa                                                                    Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 15442)                                                                              1:10    0   0   0   10  10  0                                                  1:100  0   0   0   10  3   3                                     __________________________________________________________________________

These results indicate that the test composition is capable of rapidantibacterial action in the presence of substantial amounts of organicmatter against the three human pathogens generally considered asdefinitive for antibacterial efficacy evaluation.

Example 13

The composition of Example 7 was prepared for evaluation as a skindegerming agent against resident and transient flora. Six subjects weretested using the Modified Prices Multiple Basin Technique which measuresreduction of skin flora as a percentage of that achieved by washing thehands with unmedicated soap. Bacterial counts were taken from the first,fourth and fifth basins. The counts from the first basin represent thetransient bacterial flora and that of the fourth and fifth basins theresident flora. Prior to the test, none of the subjects used a medicatedsoap for one week.

The results set forth in the following table demonstrate a very highorder of efficacy for the test composition for critical degerming usessuch as a surgical scrub for operating room personnel and skinpreparation at the surgical site.

    ______________________________________                                                      Unmedicated Soap                                                                            Test Composition                                                                         %                                                    Average No. of                                                                              Average No. of                                                                           Reduc-                                 Subject                                                                             Basin   Organisms/Basin                                                                             Organisms/Basin                                                                          tion                                   ______________________________________                                        1     1       2,500,000     60,000     97.6                                         4       1,900,000     25,000     98.7                                         5       1,300,000     15,000     98.8                                   2     1       1,700,000     30,000     98.2                                         4       1,100,000     20,000     98.2                                         5         800,000      1,000     99.9                                   3     1         800,000     40,000     95.0                                         4         600,000     20,000     96.7                                         5         500,000      1,000     99.8                                   4     1       2,000,000     50,000     97.5                                         4       1,000,000      1,000     99.9                                         5         800,000      1,000     99.9                                   5     1       1,500,000     40,000     97.3                                         4         800,000      1,000     99.9                                         5         500,000      1,000     99.8                                   6     1       1,900,000     50,000     97.4                                         4         800,000     15,000     98.1                                         5         520,000      1,000     99.8                                   ______________________________________                                    

Example 14

Oxine 2.08

Copper hydrate 0.70

Nonyl phenol/EO surfactant* 20.00

DDBSA 45.00

Isopropanol 15.00

Water (distilled) 17.22

The above composition was prepared by the procedure already describedand evaluated for efficacy against ciliated protozoan and two types ofviruses.

    ______________________________________                                        Hemaglutination Assays                                                               HA Titre                                                               Virus    Untreated  Treated (1:50)*                                                                           Treated (1:200)                               ______________________________________                                        Adenovirus                                                                             128        0           0                                             Newcastle                                                                              512        0           0                                             Disease virus                                                                 ______________________________________                                         (*1:50 and 1:200 use dilutions of composition in a water carrier in           contact with virus suspensions for 15 minutes)                           

The HA titre is a measure of the number of infectious virus particlespresent in the test suspension.

Plaque Assays

Via the same procedure as above, the untreated virus suspensionscontained 6.4×10⁴ pfu/ml of Adenovirus virus particles and 21×10⁵ pfu/mlNewcastle Disease virus particles respectively. After treatment with the1:50 and 1:200 use dilutions, readings of 0 pfu/ml were obtained. Eachpfu represents one infectious virus particle. A zero pfu readingrepresents total inactivation of the infectious virus.

Protozoan Inhibition

Inhibition of growth of ciliated protozoan (Tetrahymena) in pond waterwas obtained at a 6 ppm concentration (based on Cu-8-Q) of the abovetest composition of DDBSA and Cu-8-Q after 6-hour and 72-hour contacttimes. The 6 ppm reading represents the MIC (Minimum InhibitoryConcentration). These results demonstrate high efficacy of the testcomposition against the test microorganisms.

SECTION 7

We have also discovered than the compositions of Section 1 are usefulfor controlling plant disease by contacting plants with suchcompositions. More particularly, this embodiment of our inventionrelates to the control of plant disease and more particularly to the useof certain antimicrobial agents that are comparatively nontoxic toanimal and plant life but are highly efficaceous against fungal,bacterial and other classes of pathogens, including viruses andnematodes, which microorganisms are important casual agents of diseasein a broad spectrum of plant life.

We have found that the compositions of section 1 exhibit a wide range ofutility against fungal, bacterial and other classes of pathogenes,including viruses and nematodes, which are important casual agents ofdiseases in a broad spectrum of plant life. Such plant life includesfield and horticultural crops, ornamentals and grasses. The mode of useincludes foliar, seed, dormant season and, in some instances soiltreatment. It also includes treatments designed to preserve the plantproduct in the post-harvest period, which treatment may be carried outboth pre- and post-harvest.

The disclosed compositions present an unusual combination of propertiesthat are unexpectedly unique for control of a broad range of diseases ofa large number of plant species, including:

Antifungal control. The spectrum of activity in the use of compositionsof this invention covers the four classes of fungi--Ascomycetes,Basidiomycetes, Phycomycetes and Fungi Imperfecti.

Antibacterial control. The use of compositions of this invention coversa broad spectrum of Gram-positive and Gram-negative plant pathogens.

Antiviral and Antinematodal control. The use of compositions of thisinvention is effective against viruses and a substantial selection ofnematode species.

High antimicrobial efficacy. Minimum inhibition and minimum killconcentrations of the compositions of this invention are very low.

Low phytotoxicity. Generally, but not always, the use of the compoundsof this invention have low phytotoxicity at adequate use.

Water solubility. Concentrates prepared for use in this invention may beuse-diluted in a variety of polar and non-polar carriers, includingwater which is the most versatile. Diluted with water, the concentratesgenerally form true solutions that in most cases provide substantialhandling, mixing-for-use, application and uniformity-of-coverageadvantages over the typical water-insoluble products. In some cases ofuse-dilution, stable and often colloidal emulsions are formed. Thesegenerally provide the same advantages as true solutions.

Water insolubility. On application to the host organism (or the soil),the compositions of this invention turn insoluble in water in mostinstances, which increases antimicrobial persistence of activity andresults in increased rain wash off resistance.

Substantivity. When applied to a number of substrates, the compositionsof this invention become tightly affixed (substantive) and consequentlyexhibit substantial resistance to removal by rain or other factors.

Heat and sunlight stability. The composition of this invention exhibithigh stability to heat (to over 200° F.) and light, particularlyultraviolet.

Safety. Acute oral mammalian toxicity of the highest practicalconcentrations of the compositions of this invention is moderately low,about halfway between aspirin and common table salt. Typical usedilutions thereof, 1:100 to 1:1000 in water, are nontoxic.

Skin and eye irritation properties of typical use-dilutions range fromvery low to zero. Highest practical concentrates of the compositionsexhibit moderately high skin and eye irritation. At one-tenth of maximumconcentration, use-dilutable in the 1:10 to 1:100 range, thecompositions are inocuous to the skin and show low eye irritation.

The toxicity characteristics of the compositions exhibit two unusual andunique features of considerable practical value. First, biodegradationin most instances reduces the initially low mammalian toxicity, asapplied to the host plant or soil, up to about 95% in a few weeks afterapplication without a corresponding reduction in residual antimicrobialefficacy. Second, death in the event of accidental ingestion of a lethaldose of the compositions is a secondary and reversible mechanism whereinthe time period for initiation of medical treatment is non-critical.Medical treatments for this condition are well-known and are generallysuccessful with no adverse after effects.

High uniformity of coverage. Appropriate use-dilutions of thecompositions of this invention exhibit pronounced substrate wetting andspreading properties which provides a high degree of uniformity ofcoverage of the host plant.

Ease and economny of handling and application. The compositions of thisinvention generally are concentrated, readily pourable liquids which areeasily and rapidly misible with water for use to form either truesolutions or colloidal emulsions, as diluted for use, they are easy toapply with no settling out of active ingredients. Due to the highproduct concentration, a minimum of product need be transported, handledand stored and disposal of containers is minimized.

In the plant world, bacterial diseases are in the minority relative tofungal diseases. Surprisingly, very few products are available forbacterial disease control. This is in sharp contrast with the very largeavailability of products for fungal diseases. The antibacterials nowavailable have quite limited utility because of either low efficacy orhigh cost. Compositions of the invention exhibit considerableantibacterial promise for plant use by reason of high unit efficacy andlow cost.

The method of use and efficacy of the compositions of this invention areillustrated in the following examples.

EXAMPLES Example 1

The following composition was prepared and tested as a rice seedtreatment:

Oxine 2.05 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Octyl phenol ethoxylate (9EO) 20.00 parts by weight

Isoporpanol 20.00 parts by weight

Water 17.25 parts by weight

This composition was placed in water (800 cc per cwt. of seed) and usedto coat the inside walls of a container. Weighed seed samples wereplaced in the container which was rotated for 15 minutes to transfer thetest composition to the seed. The treated seed was stored until planted.This application procedure was repeated for application of severalcommercially available antifungal products.

Treated and untreated control seed was planted in thirteen locations infour states using both water-planting and drill-planting methods. Theeffectiveness of all tested products in increasing the seedlingemergence rate is shown below as a consolidation of results from alltest plots.

    __________________________________________________________________________            (1)   (2)      (3)    (4)                                                     Application                                                                         Improvement                                                                            Performance                                                                          Range of Improvement (%)                                Rate  over Control (%)                                                                       Consistency                                                                          High   Low                                      __________________________________________________________________________    EXAMPLE 2                                                                              4*   18.3     36.2   plus 38                                                                              plus 2                                   PRODUCT A                                                                             4     27.4     80.4   plus 56                                                                              minus 2                                  PRODUCT B                                                                             4     16.6     63.1   plus 61                                                                              minus 2                                  PRODUCT C                                                                             4     12.6     47.8   plus 32                                                                              minus 16                                 PRODUCT D                                                                             4     12.3     71.3   plus 37                                                                              minus 35                                 __________________________________________________________________________     (1) Ounces per 100 lbs. (cwt.) of rice seed of the chemical active            ingredient in all instances except Example 2 which is given in terms of       the total composition.                                                        *contains 0.1 ounce of Cu8-Q.                                                 (2) Percentage increase in seedling emergence rate as compared to that of     the untreated control seed in the thirteen test plots.                        (3) These numbers express the difference between the highest and lowest       precent change in seedling emergence rate for each test product compared      to the untreated seed results in the thriteen test plots. Thus, the lower     the number, the greater is the  testto-test consistency of emergence rate     improvement provided by the test product.                                     (4) This column lists the best (high) of the thirteen test results and th     poorest (low). "Plus" represents improvement over untreated control seed      emergence rate whereas "minus" represents a reduction therein.                Product A  a coordination product of zinc ion and manganese ethylene          bisdithiocarbamate.                                                           Product B  copper hydroxide formulated as a finely divided flowable           composition.                                                                  Product C                                                                     cisN--(1,1,2,2-tetrachloroethylthio)-4-cyclohexene-1,2-dicarboximide.         Product D  5,6dihydro-2-methyl-1,4-oxathiim-3-carboxanilide.                  The estimated costs of Products A through D range from 3 to 5 times highe     than that of the composition of Example 2.                               

Example 2

The following composition was tested for minimum fungicidalconcentration and compared to two well known antifungalchemicals--pentachlorophenol and 2,3,5 trichloro-4-propyl-sulfonylpyridine--and DDBSA.

Oxine 8.2 parts by weight

Copper hydrate 2.8 parts by weight

DDBSA 59.0 parts by weight

Propylene glycol methyl ether 30.0 parts by weight

All of the test composition concentrations to be tested wereincorporated in the fungal growth media (agar) in accordance withstandard microbiological practices. Agar plugs containing the testfungicides then were inoculated with a sporulating culture andinoculated at the temperatures and times specified by The American TypeCulture Collection (ATCC) recommendations. The plugs were then scoredfor absence or presence of organism growth. The results are shown in thefollowing table. Minimum fungicidal concentrations were determinedagainst a broad spectrum of fungi that are detrimental to man,foodstuffs and materials and which can result in metabolite formations(mycotoxins) of extreme toxicity to man and animals.

In the table below, Composition A is that of this Example 2 and theactive ingredient is Cu-8-Q; Composition B is DDBSA; Composition C ispentachlorophenol; and Composition D is 2,3,5-trichloro-4-propylsulfonylpyridine. Where no concentration is listed, no data is available. Thestated value of "1" means 1 or fewer ppm.

    ______________________________________                                                     Minimum Fungicidal Concentration                                              (ppm of active ingredient)                                                    A     B         C       D                                        ______________________________________                                        Aspergillis niger                                                                            1       10,000    1-3   --                                     (ATCC 9642)                                                                   Aspergillis terreus                                                                          1       100       --    36                                     (ATCC 10609)                                                                  Aspergillis flavus                                                                           1       1,000     22-54 --                                     (ATCC 11655)                                                                  Alternaria alternata                                                                         1       --        --    --                                     (ATCC 13963)                                                                  Aureobasidium pullulans                                                                      1       100       --    --                                     (ATCC 16624)                                                                  Lenzites trabea                                                                              1       100       1-3   --                                     (ATCC 11539)                                                                  Polyporus tulipiferae                                                                        1       100       1-3   --                                     (ATCC 11245)                                                                  Penicillium brevi                                                                            1       100       --    --                                     compactum (ATCC 16024)                                                        Rhizopus stolonifer                                                                          1       100       1-3   --                                     (ATCC 24794)                                                                  Trichoderma viride                                                                           10      100       --    --                                     (ATCC 8678)                                                                   Trichoderma sp.                                                                              1       100       --    --                                     (ATCC 12668)                                                                  Candida albicans                                                                             1       1,000     --     3                                     (ATCC 10259)                                                                  ______________________________________                                    

These results illustrate the high efficacy of the compositon of thisinvention and confirm the fact that an antifungal composition preparedfrom a Cu-8-Q/DDBSA solution is much superior to DDBSA alone. Theresults also indicate the favorable relative efficacy of the testcompositon compared to the two commercially available fungicides ofrecognized high performance.

Example 3

The compositions of this invention exhibit efficacy against a broadspectrum fungal plant pathogens, as illustrated by various use dilutionsin a water carrier of the following composition:

Copper hydrate 1.70 parts by weight

8-hydroxy quinoline 4.44 parts by weight

Isopropanol 35.00 parts by weight

DDBSA 58.86 parts by weight

A. Valencia Oranges

Tested on harvested fruit against Phomopsis stem-end rot and Diplodisrot, at a 1:100 use dilution, 2-minute dip application. After 3 weeks at70° F., the following percentages of decay were noted:

Control (untreated) oranges--9.5% decay

Treated oranges--5.3% decay

B. Sugar Cane

An agar seeding test against Ceratocystis paradoxa (pineapple disease)at a 1:10,000 (100 ppm) use dilution yielded a 3.0 mm. inhibition zone.

C. Peach Trees

Tested against Taphrina deformans (causes leaf curl disease). Four testtrees were sprayed twice, two weeks apart, with a 1:400 use dilution.Three months later, 100 leaves on each test tree were rated for leafcurl:

Control (untreated) leaves--100% leaf curl

Treated leaves--13.5% leaf curl

D. Cotton

Effectiveness against 11 fungi and 1 bacterium (Xanthomonas malvacearum)that are associated with disease of cottonseed, seedlings and otherplants was evaluated in vitro, using the following compositions:

    ______________________________________                                        Composition #1                                                                           Copper hydrate                                                                               1.70 parts by weight                                           8-hydroxy quinoline                                                                          4.44 parts by weight                                           Methanol       4.00 parts by weight                                           Isopropanol   30.86 parts by weight                                           DDBSA         59.00 parts by weight                                Composition #2                                                                           Copper hydrate                                                                               2.80 parts by weight                                           8-hydroxy quinoline                                                                          8.20 parts by weight                                           Methanol       4.00 parts by weight                                           Isopropanol   26.00 parts by weight                                           DDBSA         59.00 parts by weight                                ______________________________________                                    

Both compositions were prepared in accordance with procedures stated inprevious examples.

The following results were obtained, expressed in parts per million(ppm) of total test composition in water carrier and the relative growthinhibition provided at each test strength on each tested organism. Inthe tables below:

0=no apparent inhibition

1=some inhibition

2=considerable inhibition (little growth)

3=total inhibition (no growth)

    __________________________________________________________________________                    Composition #1   Composition #2                                               Concentrations (ppm)                                                                           Concentrations (ppm)                         Test Organisms  0 1 5 25                                                                              100                                                                              500                                                                              1000                                                                             0 1 5 25                                                                              100                                                                              500                                                                              1000                           __________________________________________________________________________    Pythium ultimum (41B)                                                                         0 0 0 1 2  3  3  0 0 1 2 2  2  2                              Rhizoctonia solani (1D)                                                                       0 0 0 1 2  3  3  0 0 1 2 2  2  2                              Fusarium (4A)   0 0 0 3 3  3  3  0 0 1 1 1  2  2                              Fusarium (4D)   0 1 1 2 2  2  3  0 0 1 1 2  2  2                              Fusarium roseum (4C)                                                                          0 0 0 1 2  2  3  0 0 0 2 2  2  2                              Colletotrichum gossypii (35A)                                                                 0 0 0 1 2  2  2  0 0 0 2 2  2  2                              Xanthomonas malvacearum (2A)                                                                  0 0 0 0 2  2  3  0 0 0 1 1  2  2                              Aspergillis sp.            1  1                                                Helminthosporium oryzae   2  2                                               Mucor mucedo               1  1                                               Penicillium sp.            1  1                                               Rhizopus sp.               1  1                                               __________________________________________________________________________

Example 4

The following composition was screened for fungal pathogen response as afoliar spray on beans and rice.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Isopropanol 32.00 parts by weight

Demineralized water 25.22 parts by weight

The rating scale is from 0 (no pathogen control) to 10 (completepathegon control). The concentration of active ingredient (in a watercarrier) of all compositions tested is 33 parts per million (ppm). Theactive ingredient in the composition of Example 4 is expressed in termsof Cu-8-Q and the chemical as listed below for four comparativeproducts. The comparative products tested were Karathane(2,4-dinitro-6-(2-octyl phenyl crotonate), Vitavax(5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide), Daconil(tetrachloroisophthalonitrile) and Maneb (manganeseethylenebisdithiocarbamate). The plants and diseases tested were beanmildew (Erysiphe polygoni), bean rust (Uromyces phaseoli typica) andrice spot (Helminthosporium orazae and Cerocospora orazae).

    ______________________________________                                                    Bean Mildew                                                                            Bean Rust Rice Spot                                      ______________________________________                                        Example 28 composition                                                                       8         10        10                                         Karathane     10         --        --                                         Vitavax       --          9        --                                         Daconil       --         --        10                                         Maneb         --         --         8                                         ______________________________________                                    

Example 5

The following composition was evaluated (diluted with water for use) invitro for inhibition against two fungal pathogens, Botrytis sp. andAlternaria sp., causal agents of a variety of plant diseases.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

The zone of inhibition agar plate test also was used to test Cunilate2174 (diluted in mineral spirits for use) for comparison. Thecomposition concentrations in the table of results below are expressedin parts per million (ppm) of Cu-8-Q. The larger the inhibition zone,the greater is the efficacy of the composition.

    ______________________________________                                                   Botrytis    Alternaria                                             ______________________________________                                        DDBSA/Cu-8-Q                                                                  Concentration (ppm)                                                                        21     50      125  21   50   125                                Inhibition zone (mm)                                                                       13     15       22   0   16    21                                Cunilate 2174                                                                 Concentration (ppm)                                                                        83     200     500  83   200  500                                Inhibition zone (mm)                                                                       13     14       16   0    0    14                                ______________________________________                                    

The DDBSA/Cu-8-Q solution of this invention exhibits an improvement inefficacy against the tested organisms by a factor of 4x in the case ofBotrytis to 10x in the case of Alternaria.

Example 6

The DDBSA/Cu-8-Q solution of the preceding example (31), diluted 1:400in a water carrier, was applied by spray nine times, at two-weekintervals, to peach and nectarine cultivars during the growing season.The results against brown rot (Monolinia fructocola), compared tonontreated trees, is presented below.

    ______________________________________                                                         % Fruit Affected                                                              Peach Nectarine                                              ______________________________________                                        At harvest (treated)                                                                              1       3                                                 At harvest (untreated)                                                                           15      43                                                 Five days later (treated)                                                                         3       6                                                 Five days later (untreated)                                                                      60      67                                                 ______________________________________                                    

Example 7

The DDBSA/Cu-8-Q solution of Example 6 was tested in vitro against amajor turf pathogen, Helminthosporium vagans, via a standard agar plateculture technique, with these results:

    ______________________________________                                                       Fungus Colony Diameter                                         ______________________________________                                        1:6700 use dilution                                                                            1         mm                                                 in water carrier                                                              1:3350 use dilution                                                                            0                                                            in water carrier                                                              Control          21        mm                                                 ______________________________________                                    

The results demonstrate very high efficacy in controlling this importantpathogen. Complete control of H. vagans was achieved in this assaybetween 3.7 and 7.5 ppm of Cu-8-Q.

As illustrated in the examples to follow, the compositions of thisinvention have high efficacy against a broad spectrum of bacteria thatare pathogenic to mammals and plant life, that contribute to reducedwater quality, that cause deterioration of foodstuffs, that degrade abroad range of manufactured and natural materials and products, andwhich generate toxic metabolites (bacteria-toxins) that are among themost poisonous substances known to man.

Of particular interest is high efficacy against Gram-negative as well asGram-positive microorganisms. Few antibacterial materials now availableare effective against the Gram-negatives and still fewer provideeconomical control of them. A number of available antibacterials toxicto Gram-negative organisms have practical limitations which severelyrestrict use, including high mammalian toxicity, phytotoxicity,corrosiveness to skin and a variety of materials, strong odor, strongcolor, high volatility, low or erratic shelf stability, low ornonexistent residual activity, and prohibition of use at elevatedtemperatures.

The basic significance in the need for Gram-negative control lies in thefact that this bacterial category includes a number of widespread,virulent pathogens which are difficult to impossible to control withpresently available antibiotics, notably Pseudomonas sp. typified byPseudomonas aeruginosa PRD-10, the standard strain in the United Statesfor evaluation of antibacterials for mandatory Gram-negative controlapplications.

The compositions herein disclosed eliminate or substantially reducethese use limitations inherent in many other germicides. Thecompositions are quite unique in having strong Gram-positive andGram-negative activity combined with broad versatility of formulationand use plus a high degree of safety (low toxicity and zero to low skinand eye irritation). Add to this the high efficacy, broad spectrumantifungal activity of the compositions of this invention and theresulting range of toxicity to target organisms and safety to man, themost sensitive of hosts, is unique indeed.

The balance of toxicity provided by this invention to Gram-positive,Gram-negative and fungal microorganisms has special value in the broadconsumer field of skin deodorancy. Present antibacterials suffer fromthe fact that they are effective primarily against Gram-positives,allowing Gram-negative and fungi overgrowth, a condition considereddangerous by many authorities.

Example 8

The DDBSA/Cu-8-Q solution of Example 2 was tested, along with a numberof well known antimicrobial agents, against a broad spectrum screen ofeconomically important Gram-positive and Gram-negative bacteria. Allantimicrobial agents were incorporated in the agar bacterial growthmedia according to standard microbiological practices. The bacterialspecies were grown in nutrient broth; 24-hour cultures, the inoculum,then were streaked onto the nutrient agar plates containing the testantimicrobials. After a 24-hour incubation at the appropriatetemperature, the plates were rated for presence or absence of bacterialgrowth.

Minimum bactericidal concentrations for each of the tested agents arestated in the following tabulation of results in parts per million (ppm)of active ingredient as defined in the description of each agent.

    __________________________________________________________________________                    Antimicrobial Agent                                                           (ppm* of active ingredient)                                   Bacteria (ATCC No.)                                                                           A   B    C  D  E   F     G                                    __________________________________________________________________________    Gram-positive:                                                                Bacillus cereus 1   100  --  7 8    5-10 --                                   Bacillus lichenforms (27326)                                                                  1   100  --  7 8   2-5   --                                   Bacillus megaterium (27327)                                                                   1   100  --  7 8   --    --                                   Bacillus subtilis (37328)                                                                     1   100  -- 750                                                                              8   --     3                                   Micrococcus flavus (10240)                                                                    1   100  --  7 8   --    --                                   Mycobacterium phlei (15610)                                                                   1    10  --  7 8   --     3                                   Staphylococcus aureus (6538)                                                                  1   100  2083                                                                              7 8   1-3    3                                   Gram-negative:                                                                Alcaligenes faecalis (337)                                                                    10  1000 -- 750                                                                              80  --    --                                   Alcaligenes marshalii (21030)                                                                 104 100  --  7 8   --    --                                   Esherichia coli (11229)                                                                       104 10,000                                                                             -- 750                                                                              80  250-500                                                                             165                                  Flavobacterium arboresceus (4358)                                                             10   10  4166                                                                              7 8   --    --                                   Klebsiella pneumoniae (4356)                                                                  10  10,000                                                                             -- 750                                                                              8   --    --                                   Proteus vulgaris                                                                              10  1000 -- 750                                                                              800 --    --                                   Pseudomonas aeruginosa (15442)                                                                104 1000 4166                                                                             750                                                                              800 1000-2500                                                                           165                                  Salmonella cholerasuis (10708)                                                                104 1000 -- 750                                                                              80  250-500                                                                             165                                  Salmonella typhi (6539)                                                                       104 1000 2083                                                                             750                                                                              80  --    165                                  __________________________________________________________________________     *stated value of "1" means 1 or less                                          A = the DDBSA/Cu8-Q solution of Example 2 with the active ingredient          expressed in terms of Cu8-Q.                                                  B = DDBSA.                                                                    C = phenol                                                                    D = Betadine, an iodine/polyvinylpyrrolidone complex containing 0.75%         iodine. The active ingredient is iodine.                                      E = Alkyl dimethyl ammonium chlorides (61% C.sub.12, 23% C.sub.14, 11%        C.sub.16 and 3% C.sub.10).                                                    F = sodium pentachlorophenate                                                  G = 2,3,5trichloro-4-propylsulfonyl pyridine.                           

These data demonstrate the high efficacy of the composition of Example2. On the basis of the average of the efficacies against all the testorganisms, Composition A is 45 times superior to Composition B; 88 timesbetter than Compositions C; 10.7 times better than Composition D; and3.5 times superior to Composition E.

On the basis of the average of the efficacies against the three testbacteria (Staphylococcus aureus, Salmonella cholerasuis and Pseudomonasaeruginosa PRD-10) required by the Environmental Protection Agency of a"hospital grade" disinfectant, Composition A is 10 times better thanComposition B; 7.2 times better than Compositions D; and 1.6 timesbetter than Composition E.

Example 9

The composition set forth below was prepared by previously describedprocedures:

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

Isopropanol 32.00 parts by weight

DDBSA 40.00 parts by weight

Water (demineralized) 25.22 parts by weight

When evaluated as a bactericide by the AOAC Use Dilution Method (12thEdition, 1975), 10 ring carriers per organism, the following resultswere obtained (A=subculture and B=resubculture):

    ______________________________________                                                    Use Dilution                                                                             Negative Positive                                                  in Water Carrier                                                                         A      B     A    B                                    ______________________________________                                        Staphylococcus aureus                                                                       1:1000       10     10  0    0                                  Salmonella cholerasuis                                                                      1:1000       10     10  0    0                                  (PRD-10)                                                                      Pseudomonas aeruginosa                                                                      1:400        10     10  0    0                                  Aerobacter aerogenes                                                                        1:400        10     10  0    0                                  ______________________________________                                    

A ten-minute kill is required against the first three pathogens for saleas a hospital grade disinfectant. Efficacy against the fourth organism,a major cause of slime in recirculated cooling water systems and pulpand paper mills, demonstrates utility of the composition as a slimicide.

Example 10

This composition was prepared and tested at one use dilution, 1:50 inwater carrier, against the causal agent of potato ring rot bacterial(Corynebacterium sepedonicum):

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

Infected potato seeds readily contaminate potato seed cutters, sacks,bins, cellars, trucks and planting equipment with the highly infectiousring rot bacteria. The result may be infected potato plants, tubers andreduced yields.

The test procedure consisted of dipping unpainted, planed wood laths(6") into a slurry of infected ring rot tuber tissue, allowing excessslurry to drain off (3-5 minutes) and then spraying the contaminatedlath with the test antibacterials. Three to five minutes later, healthyNorgold Russet potato seed pieces were rubbed vigorously against bothsides of the contaminated and antibacterial-treated laths. The processwas repeated using laths not contaminated with C. sepedonicum buttreated with the test antibacterial agent. The rubbed seed pieces werestored in bags and later planted at the appropriate time.

In addition to the composition of the invention, untreated controls, 20%Clorox (1.05% sodium hypochlorite in water), formaldehyde (37% formalindiluted 1:120 in water) and Roccal (benzalkonium chloride or zephiranchloride) diluted with water to 800 ppm concentration were tested. Theresults of the test are tabulated below and refer to plants and tubersproduced from the tubbed test seed pieces.

    ______________________________________                                                  Ring Rot %       %      %      Yield                                          Contam-  Plant   Ring Rot                                                                             Ring Rot                                                                             cwt/                                 Antimicrobial                                                                           inated   Stored  Plants Tubers acre                                 ______________________________________                                        None (control)                                                                          Yes      98      23     8      493                                  None (control)                                                                          No       95      0      0      609                                  DDBSA/    Yes      98      0      2      631                                  Cu-8-Q                                                                        DDBSA/    No       100     0      0      602                                  Cu-8-Q                                                                        20% Clorox                                                                              Yes      98      20     9      500                                  20% Clorox                                                                              No       98      0      0      602                                  Roccal    Yes      98      20     9      515                                  Roccal    No       98      0      0      638                                  ______________________________________                                    

The composition of this example demonstrates superior control of thering rot bacterium. Other species of the genus Corynebacterium arecausal agents of disease in man and a variety of plant life.

SECTION 8

According to another embodiment of our invention we have found that woodcan be preserved by treating the wood, using standard techniques such asdipping or pressurre impregnation, with a composition as set forth inSection 2 (hereinafter referred to as "the compositions of thisinvention").

DESCRIPTION OF THE PRIOR ART

Essentially, three different classes of compounds are currently beingused for the preservation of wood. These include chlorinated phenols,such as pentachlorophenol (PCP), mixed metal salts such as thosecontaining copper, chromium and arsenic (CCA salts), and petroleumdistillation by products such as creosote. These preservatives may beapplied to the surface of the wood such as by dipping or brushing or, inmore severe applications where long service life is required such aswith telephone poles, railroad ties, marine pilings, mine timbers andthe like, pressure impregnation processes are frequently used.

Basically, pressure impregnation processes are classified as either"full-cell" or "empty-cell" processes. The essential difference betweenthe two processes lies in the fact that in the full-cell process, theliquid forced into the wood is retained by the wood after impregnation.In contrast to this, in the empty-cell process, most of the treatmentfluid is expelled from the wood after impregnation. The terms "full" and"empty" derive from the fact that the cells of the wood aresubstantially filled with impregnants in the full-cell process, but tendonly to be coated with the impregnant in the empty-cell process.

The full-cell process makes use of a vacuum/pressure impregnant cycle inwhich the wood is first placed under vacuum and then, without admittingair, the treatment vessel is filled with the treatment liquid. After thewood is fully immersed in the liquid, the pressure is increased toperhaps ten atmospheres or so and the liquid is forced into the wood.After the wood has been treated to refusal, or until a predeterminedgross absorption of the treatment liquid has been achieved, the pressureis relieved and the treatment fluid is drained from the vessel. Usuallya short vacuum cycle follows to remove excess fluid from the surface ofthe wood.

The distinctive feature of the empty-cell process is that it does notmake use of an initial vacuum, but rather, as most commonly andpreferably practiced, the wood is placed under pressure prior to thetime that it is contacted with the treatment liquid. The initialpressure is maintained during the time the treatment vessel is filledwith the treatment liquid, and then the pressure is increased to asecond higher pressure, forcing the treatment liquid into the woodagainst the air pressure initially established within the wood. As aresult, when the pressure is relieved, the air compressed within thewood expels much of the liquid that was forced into the wood. Thisexpelled liquid is referred to as the "kickback". Commonly, as is thecase with the full-cell treatment, a vacuum is pulled in the treatmentvessel after the impregnation pressure has been relieved to increase therecovery of the treatment liquid and shorten the period of time in whichliquid will drip from the surface of the wood.

The empty-cell process is especially advantageous as compared with thefull-cell process when treating wood with water-borne materials sincethe wood, after treatment, is ready for economic shipment, furthertreatment, or immediate use since there is no large quantity of waterwhich must be removed as by kiln or air drying.

Numerous disadvantages attach to the use of the most commonly used woodpreservation materials, not the least among them being the more recentlyrecognized dangers to the environment and to persons and animal lifethat come in contact with the treated wood. Governmental tolerance forthe PCP, CCA salts and creosote treatment materials only exists due tothe complete absence of any alternative preservation material of proveneffectiveness to take their place. The standard treatment materials alsosuffer, to varying degrees and depending upon the particular one used,in that they sometimes are leached from the wood in service, they arenot as highly absorbed by the wood as may be desired, uniformity ofretention within the wood is variable, elevated impregnationtemperatures for purposes of efficiency can sometimes not be used,deposition of some of the materials causes embrittlement of the wood,and green lumber cannot be impregnated unless it is first dried.

SUMMARY OF THE INVENTION

Accordingly, it is a principal object of this invention to provide amethod for the preservation of wood in which the wood is treated with anantimicrobial material that is effective in preserving the wood and iscomparatively nontoxic toward animal and plant life.

Another object of this invention is to provide a method for thepreservation of wood with a comparatively nontoxic but effectiveantimicrobial that will become affixed or substantive to the wood.Another object of this invention is to provide a method whereby wood canbe treated with a preservative that is comparatively nontoxic and can beapplied utilizing standard treatment techniques including dipping,brushing, and full-cell and empty-cell pressure processes.

Another object of this invention is to provide a method for treatingwood with a preservative in which the preservative becomes affixed tothe wood, the uniformity of retention is improved, embrittlement of thewood is avoided, elevated temperatures can be used during treatment,diffusion of the preservative into green lumber can be achieved, thedanger of working with toxic chemicals can be avoided, and higher grossobsorptions and uniformity of retention can be improved.

Briefly, these and other objects of this invention are achieved bycontacting wood with a solution comprised of an antimicrobial agent thatis dissolved in a disubstituted aryl compound having an oleophilic and ahydrophilic substituent. In a preferred embodiment of this invention,for example, the antimicrobial agent can be an organometallic complexsuch as a metal chelate of 8-hydroxy-quinoline and the disubstitutedaryl compound can be an alkyl benzene acid such as a commercial grade ofDDBSA.

Use of the herein disclosed wood preservative solutions findconsiderable utility in the method of this invention by improvingsignificantly on some of the defects and encountered with the commonlyavailable wood treatment materials now in general use, such as PCP, CCAsalts and creosote. In somewhat more detail than as briefly mentionedabove, these improvements over the prior art include the following:

The compositions of this invention, when applied to wood, have a highdegree of fixation to the wood. Although the preservative compositionsas applied to or impregnated into the wood are solutions, many of thecompositions, including those based on a metal chelate of oxine, becomewater-insoluble after application and drying and become highly fixed orsubstantive to the wood the result is that they are resistant to removaleven under severe water leaching procedures.

It is known in the wood technology that when nonpolar solvent carriers,such as petroleum oils are used, these carriers penetrate the wood morequickly and provide higher retention and deeper penetration into woodthan preservatives utilizing polar carriers or solvents, such as water.The reason for the considerably greater flow rate of nonpolar liquids isnot understood, but one proposed explanation is that polar liquids, likewater, form strong hydrogen bonds which create frictional drag betweenthe wood and the liquid during flow through the pores of the wood. Atwood moisture contents below the fiber saturation point (about 30% wateron a dry wood base), flow rates of preservatives in water carriers arereduced up to 50% as compared to petroleum oils as reported in typicalstudies that have been published. Additional published studies ofwater-borne preservatives indicate that a number of these in 0.5%concentrations in water exhibit average retention reductions of up to57% compared to the retention of water alone when wood is treated viafull-cell pressure procedures. It has also been indicated that theaddition of a surface active wetting agent to water or water-bornepreservatives does not provide a to be expected increase in flow ratethrough the wood. In point of fact, the flow rate is reduced whensurfactants are used. It has been proposed that by reducing the surfacetension of the water, the rate at which the wood is swelled by the waterbecomes more rapid, with an attendant reduction in the size of the poresor passage through which the water must flow. Unlike some of thecompositions of the prior art, those of this invention do not behave inaccordance with the above observations or theory of flow. The subjectwater-borne compositions penetrate wood more rapidly, not less rapidly,than do oil-borne preservatives, and yield higher retention in the woodusing any given method of application to the wood involving significantcontacttimes between the wood and the preservation solution.

The preservatives of this invention provide for greater uniformity ofretention. Wood is a natural material which is subjected to widevariations in physical properties, not only from species to species, butwithin different portions of a single piece of wood. For this reason,piece-to-piece and within-a-piece retention of preservatives is erraticand not always satisfactory. Published information indicates that in thecase of creosote end PCP, the retentions in a given pressure treatingcharge of wood may vary as much as from 1 to 4 and sometimes evenhigher. Thus, to obtain a typical retention, it is necessary to acceptthe fact that many pieces of the wood will be grossly undertreated.Treating to a minimum retention specification is not economicallyfeasible since the cost of greatly over-treating the bulk of the woodwill be required. Thus, it is the industry practice to treat only to anaverage which undoubtedly is an important cause of premature failures inservice of, for example, utility poles, railroad ties and the like. Thecompositions of this invention exhibit a much narrower range ofretention than creosote and chlorophenol solutions. The improvement issubstantial and provides obvious performance and economic advantages.Premature failure in service from undertreatment is reduced and theimprovement allows significant reduction in average retentions at aconsiderable cost savings.

Certain of the prior art wood preservatives, such as CCA salts, aretemperature sensitive in that they will precipitate rapidly fromsolution when heated and in contact with wood. For this reason, it isknown to the industry that CCA salts should not be used in woodpreservation processes at temperatures above about 120° C. Thistemperature limitation carries two drawbacks: (1) higher operatingtemperatures which generally allow a shorter treating cycle cannot beused, and (2) since the greater of a reasonable sized piece of wood isseldom penetratd by the preservatives, especially in the case of thehard woods, the upper temperature limitation imposed through the use ofCCA salts does not permit good sterilization of the unpenetrated core.Should decay fungi be present in the wood prior to treatment, these cancontinue to grow unchecked in the untreated portion of the wood. Thismay be of little consequence if the untreated center is small crosssection, since the major contributor to wood strength is in the outertreated portion of the cross section, but in the case of species of woodthat contain comparatively large, generally impenetrable section ofheart wood, the loss of the untreated center to decay can bring aboutrapid wood failure in service. The compositions of this invention, onthe other hand, have no practical limitations as to temperatures towhich they can heated in the treatment of wood, being limited only bythe upper limit to which the wood itself can be heated without damagewhich is generally considered to be about 245° F.

As noted above, the empty-cell process has many advantages since thewood, after treatment, is not left saturated with the treatment liquid.Empty-cell processes cannot economically be practiced with any degree ofefficiency with water-borne preservatives as typified by the CCA salts.These salts are incompatible with the water-leachable materials in thewood and, as a result, the contamination contained in the kickback(particularly solid soluble sugars) causes precipitation within workingsolution of sludge-like deposits that render the working solutionuseless for further treatment. Not only does this represent asignificant economic loss, but further, due to the toxic nature of theCCA salts, a difficult disposal problem is presented. For this reason,water-borne preservatives, such as CCA salts, are generally impregnatedinto the wood using full-cell processes, despite their disadvantages,rather than accept the problem of dealing with the kickback that resultsfrom empty-cell processes. However, in the method of this invention,there is no incompatibility with the compositions of this invention andthe materials leached from the water so that no unmanageableprecipitates are collected in the kickback. Thus, in the practice ofthis invention, empty-cell processes may conveniently be used, gainingthe inherent advantages of an empty-cell treatment with a water-bornehigh -performance preservative not readily attainable in the prior art.

Certain wood preservatives, and particularly water-borne salts, tend toembrittle the wood to a degree that depends on several factors includingthe level of salt retention in the wood. No such embrittlement isimparted to the wood in the practice of the instant invention, and thismay be of considerable significance, such as in the preservation ofrailroad ties, where continued impact of high-speed rolling stock maycause rail tie failure due to the brittle nature of the wood prior tothe time that the ties would fail from microbial decay.

It is conventional to dry lumber prior to any pressure impregnationtreatment since green wood, having its cells filled with water, isessentially saturated and cannot accept impregnating fluids.Water-soluble preservatives can enter the wood by diffusion, but thisis, at best, unreliable, and at worst, of little value except at thesurface of the wood. The requirements for a water-soluble preservativethat retains its solubility during a lengthy diffusion process as isrequired with diffusion impregnation, limits the choice of preservativesto only a few permanently water-soluble toxicants such as borax and zincchloride which really cannot be considered high performancepreservatives. On the other hand, the compositions of this inventioncombine the water-solubility and sap compatibility prerequisites ofsuccessful diffusion preservative with high performance and resistanceto leaching since, after drying, the preservative of this inventionbecomes water-insoluble and affixed to the wood.

There are some applications of wood preservatives in which apreservative is applied or reapplied after a structure, such asbuilding, has been erected. Since it is physically impossible to usepressure impregnation methods in these instances, either brush or sprayapplication must be relied upon. However, since the brush or sprayapplication generally will penetrate only the surface regions of thewood, it is generally desired to increase the concentration of theactive ingredients in these treatment solutions to as high a level aspossible so that their lack of penetration will, in part, be compensatedfor by their strength. With present preservatives, there as severelimitations on the strength of the preservative treatment solution thatcan be used including, low preservative activity per unit of weight,high mammalian oral or skin toxicity, high skin and eye irritation,strong odor and color, subsequent unpaintability, flammability, and highviscoities. In contrast, in the practice of this invention, theselimitations to the use of the preservative in highly concentratedsolutions are generally eliminated, which allows the application ofsolutions with preservation efficacy or perhaps about ten times that ofthe present products per unit of weight. Due to the low toxicity, theuse of such highly concentrated solutions does not present a danger tothe health of the operator.

Example 1

The composition below was prepared.

Oxine 8.2 parts by weight

Copper hydrate 2.8 parts by weight

DDBSA 59.0 parts by weight

Propylene glycol methyl ether 30.0 parts by weight

Southern pine sapwood stakes were impregnated with the compositiondiluted 1:49 in water to a total solution retention of 42 pcf (lbs percubic foot of wood). After air-drying for 30 days, the treated3/4"×3/4"×18" long stakes were cut into 1" lengths and boiled in waterfor 4 hours. In this extremely severe leaching test, loss ofpreservative from the wood averaged 12% of that originally in the woodas measured by retained Cu-8-Q content.

Example 2

The composition of the preceding Example was diluted in water 1:19 (5%concentration). Smooth-surfaced southern pine stakes (3/4"×3/4"×18"long) were immersed in the solution for 3 minutes, as were stakes in a5% PCP solution in mineral spirits. Gross solution retentions in thewood averaged 1.7 pcf for the Example 1 composition (1.0 specificgravity) and 1.2 pcf for the PCP solution (0.82 specific gravity).Giving effect for the difference in specific gravities of the twosolutions, the weight retention of Example 1 solution was 16% higherthan the PCP solution.

Under indentical conditions of vacuum-pressure impregnation, a 5%solution of PCP in a petroleum solvent (specific gravity of 0.9) and a4% solution (1.0 specific gravity) of Example 1 composition wereemployed to treat dry southern pine stakes (3/4"×3/4"×18"). The averageretention of the former preservative was 31 pcf as compared to 42 pcffor the latter. Taking into account the specific gravity differences,the composition of Example 1 exhibited an average retention 22% higherthan the PCP solution.

Example 3

The following composition was prepared and water-diluted for use:

Oxine 4.1 parts by weight

Copper hydrate 1.4 parts by weight

DDBSA 64.0 parts by weight

Methanol 30.5 parts by weight

Also prepared were solutions of PCP in a petroleum oil. Both theforegoing composition and the PCP solution were used to pressureimpregnate 3/4"×3/4"×18" dry, smooth-surfaced southern pine stakes toseven retentions in the case of the composition of the invention and tofour retentions for the PCP ingredient concentration in solution wasadjusted to yield the desired retention on the basis of an average of 42pcf total solution pickup in the case of the above composition and 31pcf in the case of the PCP solutions. The retentions hereafter arereported in terms of total weight of the above composition and PCP.

A full cell vacuum-pressure treatment procedure was used. The retortcharge per retention was 100 stakes. Treatment operating schedule wasthe same for both types of preservative solutions in all retentions.

Weighing each stake before and after pressure treatment yielded theseresults:

    ______________________________________                                                                Low to High                                                     Retention Range (pcf)                                                                       Difference (%)                                        ______________________________________                                        (A)   Example 3                                                                     Charge #1 0.29 to 0.37    28                                                  Charge #2 0.32 to 0.42    31                                                  Charge #3 0.52 to 0.72    38                                                  Charge #4 0.68 to 0.97    43                                                  Charge #5 1.00 to 1.28    28                                                  Charge #6 1.05 to 1.43    36                                                  Charge #7 1.44 to 1.78    24                                                                            33   Average                                  (B)   PCP                                                                           Charge #1 0.16 to 0.25    56                                                  Charge #2 0.27 to 0.49    81                                                  Charge #3 0.32 to 0.67    109                                                 Charge #4 0.43 to 0.92    114                                                                           90   Average                                  ______________________________________                                    

The foregoing retention ranges represent the spread from the lowest tothe highest retention obtained in the treatment of each 100 stakecharge.

The improvement in retention uniformity of the compositions of thisExample compared to PCP is large, both as to individual charges andoverall averages. Of further note to the relatively uniform spread inthe high-low differences from charge-to-charge in the case of thisExample whereas in the case of PCP, the retention range is progressivelylarger as the average retention increases. This is of significance sincethe composition of this Example is normally used in the 0.2 to 0.6 pcfrange whereas the normal use retention of PCP is 0.4 to 0.6 pcf. Theaverage high-low spread, therefore, in the most-used retention range is32% versus over 100% for PCP.

Example 4

The composition of Example 1 was diluted 1:9 and 1:99 in water andheated to 210° F. for 24 hours in a closed reflux system. No appearancedifference was noted before and after the heating period, either at 210°F. and after cooling the solutions to room temperature.

Freshly prepared 1:9 and 1:99 use dilutions were then maintained at 210°F. 24-hours with the solutions separately containing green and drysouthern pine wood (10 gms of wood per 100 gms of test solution). Nosolution appearance changes were noted.

Southern pine sap was obtained by compressing fresh-sawn green pine at2000 psi and collecting the discharged sap. A 1:49 use dilution ofExample 1 composition was prepared and admixed with pine sap in threeweight ratios: 1 to 2, 1 to 1, and 2 to 1. After 4-hours heating at 210°F., no appearance charge was noted. After 3-month storage at roomtemperature, no appearance charge was noted.

All solutions, before and after the test procedures were transparent,true solutions. All solutions after the test procedures exhibited nosignificant change in active ingredient content.

Example 5

Fresh cut green southern pine sapwood stakes (1"×1"×72" long) were dipimmersed into an 8% water solution of the Composition Example 1, in avertical position, allowing the top 24" of the stake to remain above thelevel of the solution. After one-week, the stakes were removed and cutinto 6" lengths and the cross-section of each piece qualitativelychecked for depth and uniformity of preservative penetration. All piecesoriginally immersed in the solutionn exhibited complete and essentiallyuniform penetration as measured by color change from natural wood toblack, from the placement on the wood of a 1% dithio oxamide (a copperindicator) in isopropanol.

In addition, preservative penetration completely through the crosssection of the stakes occurred up to about 10" above the point ofimmersion.

SECTION 9

According to another embodiment of our invention we have discovered amethod for the preservation of foodstuffs and the prevention ofmammalian diseases caused by contaminated food which involves using thecomposition of Section 1 (hereinafter referred to as "the compositionsof this invention").

More particularly, this invention relates to the preservation offoodstuffs and to methods for the treatment of raw and preparedfoodstuffs as well as food handling equipment and packaging materials toprevent spoilage and mammalian diseases caused by pathogens.

DESCRIPTION OF THE PRIOR ART

For many years antimicrobial compositions have been used in thetreatment of foodstuffs to prevent their deterioration and to preventdiseases in humans and animals that may be caused by food contamination.These antimicrobials have been used not only in treating raw andfinished food products, but also to prevent contamination that may beoccasioned by the use of unclean handling and transportation facilitiesand packaging materials.

The problem of the preservation of food and the danger to mammals causedby contaminated food has been an age-old problem. Some authorities havestated that more people in the Middle Ages died of ergot poisoning, atoxic fungal metabolite of rye cereal grain, than of the plague. Eventoday it has been suggested by some authorities that food poisoning maycause some 90% of all human illness.

Since foodstuffs are intended to be ingested by humans and animals, itgoes without saying that the safety of their use and low toxicity areessential considerations. This fact has severely limited theavailability of known antimicrobials for food use. The antimicrobialsthat currently find favor and are sanctioned for use generally are of alow order of efficacy which frequently results in a highcost-to-performance ratio, particularly when used on raw foodstuffs forpreservation.

Mycotoxin formation in raw plant foods is a cause of growing concern.Those produced by certain Aspergillis, Penicillium, Alternaria,Trichoderma, Helminthosporium and other fungi are among the most toxicsubstances known to man and are potent carcinogens, teratogens andtremorgens. Proper handling and storage conditions drastically reduce,if not eliminate, these fungi, and hence the production of dangeroustoxins. But even in the industrial nations, it is virtually impossibleto effect adequate control over hundreds of millions of tons ofagricultural products which are grown, handled and stored by millions ofpersons. The result is varying degrees of fungal growth on a significantportion of the total. Subsequent processing generally destroys the fungibut not the mycotoxins.

Incidence of adverse effects on humans of mycotoxins in food isdifficult to assess in the high technology nations, but is readilyapparent in a number of the undeveloped tropical areas where veryfavorable mold growth conditions are coupled with few safeguards.

Incidence of animal, particularly livestock, disease from both fungi andmycotoxins usually is higher than for humans. Some livestock and poultrydiseases, caused by consumption of moldy feed, cause serious economiclosses. Aflatoxin M, an extremely toxic mycotoxin, has been found in themilk of cows that have eaten moldy grain.

OBJECTS OF THE INVENTION

Accordingly, it is an object of this invention to provide methods forthe treatment of raw and prepared foodstuffs that are effective toprevent food deterioration and diseases in mammals through the use ofantimicrobial compositions that are generally nontoxic to animal andplant life.

Another object of this invention is to provide for the use ofantimicrobial compositions that are comparatively nontoxic to animal andplant life, but which are highly efficacious in destroyingmicroorganisms that cause food spoilage and disease-causing organisms.

Briefly, these and other objects of this invention are achieved bytreating foodstuffs and handling equipment and packaging materials thatcome in contact with foodstuffs with a composition according to Section1.

DESCRIPTION OF THE INVENTION

The compositions of this invention have unique utility for foodstuffpreservation by reason of safety, antifungal and antibacterial efficacythat may be orders of magnitude superior to current materials, and hasvirtually no color, odor or taste in use concentrations. Additionalfeatures include residual persistence, low volatility, high heat andsunlight stability and water insolubility after application, andexcellent economy of use.

Among the suitable preservative applications for compositions of theinvention, the following may be mentioned:

(1) Fresh fruit, vegetables and nuts;

(2) Dried fruits and vegetables during the dehydration process;

(3) Cereal grains for human, animal and poultry consumption;

(4) Animal silage;

(5) Prepared foodstuffs;

(6) Meat, fish and dairy products;

(7) Fruit and vegetable juices and fruit condiments; and

(8) Handling and processing equipment, storage and transportationfacilities, and packaging materials for foodstuffs.

The most used preservatives typically are sanctioned in the 100 to 1,000ppm concentration range in foodstuffs. These preservatives have acuteoral LD₅₀ toxicities in the 100 to 5,000 mg/kg range. By contrast, theconcentrates of this invention, exhibiting an LD₅₀ of 1,500, areeffective generally for preservation in the range of 1 to 25 ppm againstboth fungal and bacterial attack. When the concentrates are diluted forefficacious use, they may display LD₅₀ toxicities above about 20,000mg/kg. Therefore, the compositions of the invention have considerablylower toxicity in adequate use concentrations than present foodpreservatives.

The following examples demonstrate the utility of this invention for avariety of food preservation applications:

EXAMPLES Example 1

The following composition was prepared and tested for control of fungalgrowth on an outside, exposed-to-the-weather concrete slab which wascovered completely at the start of the test with black fungal growth ofunknown species (amounts are parts by weight):

Oxine 4.4

Copper hydrate 1.5

DDBSA 64.0

Methanol 30.1

After 1:150 use dilution in water, the composition was applied to theconcrete slab by spraying to run-off. Within six months the black fungalgrowth had completely disappeared and no regrowth was noted during atwo-year observation period thereafter. The six-month period toinitially remove the fungi is believed to be that required for the deadorganisms to dry, break up and become unadhered to the concrete, andfinally, to be washed away by rain.

In summary, the compositions of this invention provide both a spectrumand a magnitude of performance against plant and mammalian pathogensseldom seen in any antimicrobial and heretofore unknown in one safeenough for foodstuff use.

Examples 2-9

Examples 2 through 9 that follow illustrate the broad spectrum of thecompositions of this invention for controlling fungi that causefoodstuff spoilage, that are pathogenic to mammals, and that producedangerous mycotoxins.

Example 2

The following composition was tested for minimum fungicidalconcentration and compared to two well known antifungalchemicals--pentachlorophenol and 2,3,5 trichloro-4-propyl-sulfonylpyridine--and DDBSA.

Oxine 8.2 parts by weight

Copper hydrate 2.8 parts by weight

DDBSA 59.0 parts by weight

Propylene glycol methyl ether 30.0 parts by weight

All of the test composition concentrations to be tested wereincorporated in the fungal growth media (agar) in accordance withstandard microbiological practices. Agar plugs containing the testfungicides then were inoculated with a sporulating culture andinoculated at the temperatures and times specified by The American TypeCulture Collection (ATCC) recommendations. The plugs were then scoredfor absence or presence of organism growth. The results are shown in thefollowing table. Minimum fungicidal concentrations were determinedagainst a broad spectrum of fungi that are detrimental to man,foodstuffs and materials and which can result in metabolite formations(mycotoxins) of extreme toxicity to man and animals.

In the table below, Composition A is that of this Example 2 and theactive ingredient is Cu-8-Q; Composition B is DDBSA; Composition C ispentachlorophenol; and Composition D is 2,3,5-trichloro-4-propylsulfonylpyridine. Where no concentration is listed, no data is available. Thestated value of "1" means 1 or fewer ppm.

    ______________________________________                                                    Minimum Fungicidal Concentration                                              (ppm of active ingredient)                                                     A    B         C        D                                        ______________________________________                                        Aspergillis niger                                                                            1      10,000    1-3    --                                     (ATCC 9642)                                                                   Aspergillis terreus                                                                          1      100       --     36                                     (ATCC 10609)                                                                  Aspergillis flavus                                                                           1      1,000     22-54  --                                     (ATCC 11655)                                                                  Alternaria alternata                                                                         1      --        --     --                                     (ATCC 13963)                                                                  Aureobasidium pullulans                                                                      1      100       --     --                                     (ATCC 16624)                                                                  Lenzites trabea                                                                              1      100       1-3    --                                     (ATCC 11539)                                                                  Polyporus tulipiferae                                                                        1      100       1-3    --                                     (ATCC 11245)                                                                  Penicillium breyl                                                                            1      100       --     --                                     compactum (ATCC 16024)                                                        Rhizopus stolonifer                                                                          1      100       1-3    --                                     (ATCC 24794)                                                                  Trichoderma viride                                                                           10     100       --     --                                     (ATCC 8678)                                                                   Trichoderma sp.                                                                              1      100       --     --                                     (ATCC 12668)                                                                  Candida albicans                                                                             1      1,000     --      3                                     (ATCC 10259)                                                                  ______________________________________                                    

These results illustrate the high efficacy of the composition of thisinvention and confirm the fact that an antifungal composition preparedfrom a Cu-8-Q/DDBSA solution is much superior to DDBSA alone. Theresults also indicate the favorable relative efficacy of the testcomposition compared to the two commercially available fungicides ofrecognized high performance.

Example 3

The purpose of this test was to determine antifungal efficacy ofDDBSA/Cu-8-Q solutions and to compare their efficacy to that of a worldstandard, sodium pentachlorophenate, and a mixture of two well-knownagricultural fungicides, Topsin M (a thiophenate) and Nabam (athiocarbomate). The test method is designated as a proposal for theFinnish NWPC Standard No. 1.4.1.3/1974. The test substrate was freshcut, green pine wood. The test fungi were:

Blue stain fungi--mixture of Ceratocystis pilifera Z11 Sclerophomaentoxylina Z17 Pullularia pullulans U2

Mold fungi--mixture of Paecilomyces varioti X15 Cladosporiumsphaerospermum R7 Aspergillis amstelodami X19

In the table below, Composition A is formulation comprised of 64 wt. %DDBSA, 5 wt. % Cu-8-Q and 31 wt. % methanol diluted 1:200 with a watercarrier.

Composition B is the same formulation diluted 1:100 with a watercarrier.

Composition C is a 1.5% concentration of sodium pentachlorophenate inwater.

Composition D is a 0.4% concentration in water of a 47:53 weight ratioof Topsin M:Nabam.

E refers to untreated control pine boards.

The rating index is:

0=no visible growth

1=traces of growth

2=slight growth

3=moderate growth

4=covered with fungi

    ______________________________________                                                      Test Composition                                                              A     B     C       D   E                                       ______________________________________                                        Blue stain fungi growth                                                                       0.8     0.3   0.5   2.5 3.9                                   Mold fungi growth                                                                             0.5     0     0.3   1.3 3.6                                   ______________________________________                                    

The demonstrated efficacy of Compositions A and B against the six listedfungal organisms has utility not only on the tested substrate--wood--butalso for protection of a variety of other materials that are attacked byone or more of the fungi, including paint, concrete, brick, textiles andleather.

Example 4

Using the standard AOAC fungicidal test method (12th Edition, 1975), thecomposition below was evaluated against two widespread fungi.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Isopropanol 32.00 parts by weight

Demineralized water 25.22 parts by weight

The two fungi were Aspergillis niger, a ubiquitous black fungus whichflourishes on a broad range of substrates, and Trichophytonmentagrophytes, a cause of "athlete's foot."

A. niger--at 1:200 use dilution in a water carrier, no growth after 10minutes' exposure.

T. mentagrophytes--at 1:750 use dilution in a water carrier, no growthafter 10 minutes' exposure.

Simular but somewhat lower efficacy results were obtained bysubstituting zinc-8-Q or aluminum-8-Q in the composition of thisexample, produced by reacting zinc oxide and aluminum hydroxiderespectively with oxine.

Example 5

The compositions of this invention exhibit efficacy against a broadspectrum fungal plant pathogens, as illustrated by various use dilutionsin a water carrier of the following composition:

Copper hydrate 1.70 parts by weight

8-hydroxy quinoline 4.44 parts by weight

Isopropanol 35.00 parts by weight

DDBSA 58.86 parts by weight

A. Valencia Oranges

Tested on harvested fruit against Phomopsis stem-end rot and Diplodisrot, at a 1:100 use dilution, 2-minute dip application. After 3 weeks at70° F., the following percentages of decay were noted:

Control (untreated) oranges--9.5% decay

Treated oranges--5.3% decay

B. Sugar Cane

An agar seeding test against Ceratocystis paradoxa (pineapple disease)at a 1:10,000 (100 ppm) use dilution yielded a 3.0 mm. inhibition zone.

C. Peach Trees

Tested against Taphrina deformans (causes leaf curl disease). Four testtrees were sprayed twice, two weeks apart, with a 1:400 use dilution.Three months later, 100 leaves on each test tree were rated for leafcurl:

Control (untreated) leaves--100% leaf curl

Treated leaves--13.5% leaf curl

D. Cotton

Effectiveness against 11 fungi and 1 bacterium (Xanthomonas malvacearum)that are associated with disease of cottonseed, seedlings and otherplants was evaluated in vitro, using the following compositions:

    ______________________________________                                        Composition #1                                                                           Copper hydrate                                                                              1.70 parts by weight                                            8-hydroxy quinoline                                                                         4.44 parts by weight                                            Methanol      4.00 parts by weight                                            Isopropanol   30.86 parts by weight                                           DDBSA         59.00 parts by weight                                Composition #2                                                                           Copper hydrate                                                                              2.80 parts by weight                                            8-hydroxy quinoline                                                                         8.20 parts by weight                                            Methanol      4.00 parts by weight                                            Isopropanol   26.00 parts by weight                                           DDBSA         59.00 parts by weight                                ______________________________________                                    

Both compositions were prepared in accordance with procedures stated inprevious examples.

The following results were obtained, expressed in parts per million(ppm) of total test composition in water carrier and the relative growthinhibition provided at each test strength on each tested organism. Inthe tables below:

0=no apparent inhibition

1=some inhibition

2=considerable inhibition (little growth)

3=total inhibition (no growth)

    __________________________________________________________________________                    Composition #1   Composition #2                                               Concentrations (ppm)                                                                           Concentrations (ppm)                         Test Organisms  0 1 5 25                                                                              100                                                                              500                                                                              1000                                                                             0 1 5 25                                                                              100                                                                              500                                                                              1000                           __________________________________________________________________________    Pythium ultimum (41B)                                                                         0 0 0 1 2  3  3  0 0 1 2 2  2  2                              Rhizoctonia solani (1D)                                                                       0 0 0 1 2  3  3  0 0 1 2 2  2  2                              Fusarium (4A)   0 0 0 3 3  3  3  0 0 1 1 1  2  2                              Fusarium (4D)   0 1 1 2 2  2  3  0 0 1 1 2  2  2                              Fusarium roseum (4C)                                                                          0 0 0 1 2  2  3  0 0 0 2 2  2  2                              Colletotrichum gossypii (35A)                                                                 0 0 0 1 2  2  2  0 0 0 2 2  2  2                              Xanthomonas malvacearum (2A)                                                                  0 0 0 0 2  2  3  0 0 0 1 1  2  2                              Aspergillis sp.            1  1                                                Helminthosporium oryzae   2  2                                               Mucor mucedo               1  1                                               Penicillium sp.            1  1                                               Rhizopus sp.               1  1                                               __________________________________________________________________________

Example 6

The composition of Example 4 was screened for fungal pathogen responseas a foliar spray on beans and rice. The rating scale is from 0 (nopathogen control) to 10 (complete pathogen control). The concentrationof active ingredient (in a water carrier) of all compositions tested is33 parts per million (ppm). The active ingredient in the composition ofExample 4 is expressed in terms of Cu-8-Q and the chemical as listedbelow for four comparative products. The comparative products testedwere Karathane (2,4-dinitro-6-(2-octyl phenyl crotonate), Vitavax(5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide), Daconil(tetrachloroisophthalonitrile) and Maneb (manganeseethylenebisdithiocarbamate). The plants and diseases tested were beanmildew (Erysiphe polygoni), bean rust (Uromyces phaseoli typica) andrice spot (Helminthosporium orazae and Cerocospora orazae).

    ______________________________________                                                    Bean Mildew                                                                            Bean Rust Rice Spot                                      ______________________________________                                        Example 28 composition                                                                       8         10        10                                         Karathane     10         --        --                                         Vitavax       --          9        --                                         Daconil       --         --        10                                         Maneb         --         --         8                                         ______________________________________                                    

Example 7

The following composition was evaluated (diluted with water for use) invitro for inhibition against two fungal pathogens, Botrytis sp. andAlternaria sp., causal agents of a variety of plant diseases.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

The zone of inhibition agar plate test also was used to test Cunilate2174 (diluted in mineral spirits for use) for comparison. Thecomposition concentrations in the table of results below are expressedin parts per million (ppm) of Cu-8-Q. The larger the inhibition zone,the greater is the efficacy of the composition.

    ______________________________________                                                   Botrytis    Alternaria                                             ______________________________________                                        DDBSA/Cu-8-Q                                                                  Concentration (ppm)                                                                        21     50      125  21   50   125                                Inhibition zone (mm)                                                                       13     15       22   0   16    21                                Cunilate 2174                                                                 Concentration (ppm)                                                                        83     200     500  83   200  500                                Inhibition zone (mm)                                                                       13     14       16   0    0    14                                ______________________________________                                    

The DDBSA/Cu-8-Q solution of this invention exhibits an improvement inefficacy against the tested organisms by a facor of 4x in the case ofBotrytis to 10x in the case of Alternaria.

Example 8

The DDBSA/Cu-8-Q solution of the preceding example (31), diluted 1:400in a water carrier, was applied by spray nine times, at two-weekintervals, to peach and nectarine culivars during the growing season.The results against brown rot (Monolinia fructocola), compared tonontreated trees, is presented below.

    ______________________________________                                                         % Fruit Affected                                                              Peach Nectarine                                              ______________________________________                                        At harvest (treated)                                                                              1       3                                                 At harvest (untreated)                                                                           15      43                                                 Five days later (treated)                                                                         3       6                                                 Five days later (untreated)                                                                      60      67                                                 ______________________________________                                    

Example 9

The DDBSA/Cu-8-Q solution of Example 8 was tested in vitro against amajor turf pathogen, Helminthosporium vagans, via a standard agar plateculture technique, with these results:

    ______________________________________                                                       Fungus Colony Diameter                                         ______________________________________                                        1:6700 use dilution                                                                            1         mm                                                 in water carrier                                                              1:3350 use dilution                                                                            0                                                            in water carrier                                                              Control          21        mm                                                 ______________________________________                                    

The results demonstrate very high efficacy in controlling this importantpathogen. Complete control of H. vagans was achieved in this assaybetween 3.7 and 7.5 ppm of Cu-8-Q.

As illustrated in the examples to follow, the compositions of thisinvention have high efficacy against a broad spectrum of bacteria thatare pathogenic to mammals and plant life, that contribute to reducedwater quality, that cause deterioration of foodstuffs, that degrade abroad range of manufactured and natural materials and products, andwhich generate toxic metabolites (bacteria-toxins) that are among themost poisonous substances known to man.

Of particular interest is high efficacy against Gram-negative as well asGram-positive microorganisms. Few antibacterial materials now availableare effective against the Gram-negatives and still fewer provideeconomical control of them. A number of available antibacterials toxicto Gram-negative organisms have practical limitations which severelyrestrict use, including high mammalian toxicity, phytotoxicity,corrosiveness to skin and a variety of materials, strong odor, strongcolor, high volatility, low or erratic shelf stability, low ornonexistent residual activity, and prohibition of use at elevatedtemperatures.

The basic significance in the need for Gram-negative control lies in thefact that this bacterial category includes a number of widespread,virulent pathogens which are difficult to impossible to control withpresently available antibiotics, notably Pseudomonas sp. typified byPseudomonas aeruginosa PRD-10, the standard strain in the United Statesfor evaluation of antibacterials for mandatory Gram-negative controlapplications.

The compositions herein disclosed eliminate or substantially reducethese use limitations inherent in many other germicides. Thecompositions are quite unique in having strong Gram-positive andGram-negative activity combined with broad versatility of formulationand use plus a high degree of safety (low toxicity and zero to low skinand eye irritation). Add to this the high efficacy, broad spectrumantifungal activity of the compositions of this invention and theresulting range of toxicity to target organisms and safety to man, themost sensitive of hosts, is unique indeed.

The balance of toxicity provided by this invention to Gram-positive,Gram-negative and fungal microorganisms has special value in the broadconsumer field of skin deodorancy. Present antibacterials suffer fromthe fact that they are effective primarily against Gram-positives,allowing Gram-negative and fungi overgrowth, a condition considereddangerous by many authorities.

Example 10

The DDBSA/Cu-8-Q solution of Example 2 was tested, along with a numberof well known antimicrobial agents, against a broad spectrum screen ofeconomically important Gram-positive and Gram-negative bacteria. Allantimicrobial agents were incorporated in the agar bacterial growthmedia according to standard microbiological practices. The bacterialspecies were grown in nutrient broth; 24-hour cultures, the inoculum,then were streaked onto the nutrient agar plates containing the testantimicrobials. After a 24-hour incubation at the appropriatetemperature, the plates were rated for presence or absence of bacterialgrowth.

Minimum bactericidal concentrations for each of the tested agents arestated in the following tabulation of results in parts per million (ppm)of active ingredient as defined in the description of each agent.

    __________________________________________________________________________                    Antimicrobial Agent                                                           (ppm* of active ingredient)                                   Bacteria (ATCC No.)                                                                           A   B    C  D  E   F     G                                    __________________________________________________________________________    Gram-positive:                                                                Bacillus cereus 1   100  --  7 8    5-10 --                                   Bacillus lichenforms (27326)                                                                  1   100  --  7 8   2-5   --                                   Bacillus megaterium (27327)                                                                   1   100  --  7 8   --    --                                   Bacillus subtilis (37328)                                                                     1   100  -- 750                                                                              8   --     3                                   Micrococcus flavus (10240)                                                                    1   100  --  7 8   --    --                                   Mycobacterium phlei (15610)                                                                   1    10  --  7 8   --     3                                   Staphylococcus aureus (6538)                                                                  1   100  2083                                                                              7 8   1-3    3                                   Gram-negative:                                                                Alcaligenes faecalis (337)                                                                    10  1000 -- 750                                                                              80  --    --                                   Alcaligenes marshalii (21030)                                                                 104 100  --  7 8   --    --                                   Esherichia coli (11229)                                                                       104 10,000                                                                             -- 750                                                                              80  250-500                                                                             165                                  Flavobacterium arboresceus (4358)                                                             10   10  4166                                                                              7 8   --    --                                   Klebsiella pneumoniae (4356)                                                                  10  10,000                                                                             -- 750                                                                              8   --    --                                   Proteus vulgaris                                                                              10  1000 -- 750                                                                              800 --    --                                   Pseudomonas aeruginosa (15442)                                                                104 1000 4166                                                                             750                                                                              800 1000-2500                                                                           165                                  Salmonella cholerasuis (10708)                                                                104 1000 -- 750                                                                              80  250-500                                                                             165                                  Salmonella typhi (6539)                                                                       104 1000 2083                                                                             750                                                                              80  --    165                                  __________________________________________________________________________     *stated value of "1" means 1 or less                                          A = the DDBSA/Cu8-Q solution of Example 2 with the active ingredient          expressed in terms of Cu8-Q.                                                  B = DDBSA.                                                                    C = phenol                                                                    D = Betadine, an iodine/polyvinylpyrrolidone complex containing 0.75%         iodine. The active ingredient is iodine.                                      E = Alkyl dimethyl ammonium chlorides (61% C.sub.12, 23% C.sub.14, 11%        C.sub.16 and 3% C.sub.10).                                                    F = sodium pentachlorophenate                                                  G = 2,3,5trichloro-4-propylsulfonyl pyridine.                           

These data demonstrate the high efficacy of the composition of Example2. On the basis of the average of the efficacies against all the testorganisms, Composition A is 45 times superior to Composition B; 88 timesbetter than Composition C; 10.7 times better than Composition D; and 3.5times superior to Composition E.

On the basis of the average of the efficacies against the three testbacteria (Staphylococcus aureus, Salmonella cholerasuis and Pseudomonasaeruginosa PRD-10) required by the Environmental Protection Agency of a"hospital grade" disinfectant, Composition A is 10 times better thanComposition B; 7.2 times better than Composition D; and 1.6 times betterthan Composition E.

Example 11

The composition set forth below was prepared by previously describedprocedures:

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

Isopropanol 32.00 parts by weight

DDBSA 40.00 parts by weight

Water (demineralized) 25.22 parts by weight

When evaluated as a bactericide by the AOAC Use Dilution Method (12thEdition, 1975), 10 ring carriers per organism, the following resultswere obtained (A=subculture and B=resubculture):

    ______________________________________                                                    Use Dilution                                                                             Negative Positive                                                  In Water Carrier                                                                         A      B     A    B                                    ______________________________________                                        Staphylococcus aureus                                                                       1:1000       10     10  0    0                                  Salmonella cholerasuis                                                                      1:1000       10     10  0    0                                  (PRD-10)                                                                      Pseudomonas aeruginosa                                                                      1:400        10     10  0    0                                  Aerobacter aerogenes                                                                        1:400        10     10  0    0                                  ______________________________________                                    

A ten-minute kill is required against the first three pathogens for saleas a hospital grade disinfectant. Efficacy against the fourth organism,a major cause of slime in recirculated cooling water systems and pulpand paper mills, demonstrates utility of the composition as a slimicide.

Example 12

This composition was prepared and tested at one use dilution, 1:50 inwater carrier, against the causal agent of potato ring rot bacteria(Corynebacterium sepedonicum):

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

Infected potato seed readily contaminate potato seed cutters, sacks,bins, cellars, trucks and planting equipment with the highly infectiousring rot bacteria. The result may be infected potato plants, tubers andreduced yields.

The test procedure consisted of dipping unpainted, planed wood laths(6") into a slurry of infected ring rot tuber tissue, allowing excessslurry to drain off (3-5 minutes) and then spraying the contaminatedlath with the test antibacterials. Three to five minutes later, healthyNorgold Russet potato seed pieces were rubbed vigorously against bothsides of the contaminated and antibacterial-treated laths. The processwas repeated using laths not contaminated with C. sepedonicum buttreated with the test antibacterial agent. The rubbed seed pieces werestored in bags and later planted at the appropriate time.

In addition to the composition of the invention, untreated controls, 20%Clorox (1.05% sodium hypochlorite in water), formaldehyde (37% formalindiluted 1:120 in water) and Roccal (benzalkonium chloride or zephiranchloride) diluted with water to 800 ppm concentration were tested. Theresults of the test are tabulated below and refer to plants and tubersproduced from the tubbed test seed pieces.

    ______________________________________                                                  Ring Rot %       %      %      Yield                                          Contam-  Plant   Ring Rot                                                                             Ring Rot                                                                             cwt/                                 Antimicrobial                                                                           inated   Stored  Plants Tubers acre                                 ______________________________________                                        None (control)                                                                          Yes      98      23     8      493                                  None (control)                                                                          No       95      0      0      609                                  DDBSA/    Yes      98      0      2      631                                  Cu-8-Q                                                                        DDBSA/    No       100     0      0      602                                  Cu-8-Q                                                                        20% Clorox                                                                              Yes      98      20     9      500                                  20% Clorox                                                                              No       98      0      0      602                                  Roccal    Yes      98      20     9      515                                  Roccal    No       98      0      0      638                                  ______________________________________                                    

The composition of this example demonstrates superior control of thering rot bacterium. Other species of the genus Corynebacterium arecausal agents of disease in man and a variety of plant life.

Example 13

The composition below was prepared and tested for speed and range ofantibacterial activity, in the absence and presence of organic matter(blood) for use in hospital disinfection, cold sterilization andantisepsis.

Oxine 4.1 parts by weight

Copper hydrate 1.4 parts by weight

DDBSA 65.0 parts by weight

Propylene glycol methyl ether 29.5 parts by weight

Many antimicrobial agents are partially or totally deactivated in thepresence of organic matter, constituting a severe limitation toeffectiveness of such agents for a number of uses such as woundantisepsis and medical instrumentation and surface disinfection wherelarge amounts of organic matter often are encountered and sometimes areunavoidable.

The AOAC Use Dilution Confirmation Test (12th Edition, 1970) wasmodified as follows:

(a) The test temperature was 37° C.

(b) The ring carriers were soaked in sheep blood for two hours,air-dried for one hour, then contaminated with the test pathogen.

(c) The contaminated rings were contacted with the test antibacterialagent for 30-second, one-minute and three-minute periods.

The results are set forth in the following table, in which:

0=no growth in 10 of 10 tubes tested

1=growth in 1 of 10 tubes tested

2=growth in 2 of 10 tubes tested

3=growth in 3 of 10 tubes tested etc.

    __________________________________________________________________________                Use Dilution in                                                                       In Absence of Blood                                                                       In Presence of Blood                          Test Pathogen                                                                             Water Carrier                                                                         30 sec.                                                                           1 min.                                                                            3 min.                                                                            30 sec.                                                                           1 min.                                                                            3 min.                                __________________________________________________________________________    Staphylococcus aureus                                                                     Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 6538) 1:10    0   0   0   0   0   0                                                  1:100  0   0   0   3   6   3                                     Salmonella typhi                                                                          Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 6539) 1:10    0   0   0   0   0   0                                                 1:00    0   0   0   0   0   0                                     Pseudomonas aeruginosa                                                                    Undiluted                                                                             0   0   0   0   0   0                                     (ATCC 15442)                                                                              1:10    0   0   0   10  10  0                                                  1:100  0   0   0   10  3   3                                     __________________________________________________________________________

These results indicate that the test composition is capable of rapidantibacterial action in the presence of substantial amounts of organicmatter against the three human pathogens generally considered asdefinitive for antibacterial efficacy evaluation.

Example 14

The following DDBSA/Cu-8-Q solution was prepared in accordance withpreviously stated techniques. (In this instance, Cu-8-Q was formed insitu from copper hydrate and oxine, also known as 8-hydroxy quinoline.)

Copper hydrate 1.70

Oxine 4.44

DDBSA 64.81

Methanol 15.05

Isopropanol 14.00

This composition was diluted with a water carrier, as tabularized below,and tested in comparison with a sodium tetrachlorophenate (23%) liquidconcentrate, also diluted in a water carrier, against organisms on threespecies of green lumber--Douglas fir, Amabilis fir and Ponderosa pine.The organisms were:

Cephaloascus fragans a brown mold that infects certain wood species

Trichoderma virgatum a common cold

Mixed spores a combination of two molds (Penicillium sp. and Aspergillisniger) and a fungus (Ceratocystis pilifera that causes blue stain inwood.

The freshly cut wood samples were dip treated (15-second immersion) withthe test fungicides and then innoculated with spore suspensions of theabove-described fungi. The test boards plus untreated control boardswere then placed in a warm, humid chamber for four weeks. The resultsare set forth in the table below in which:

    ______________________________________                                                                           Mixed                                              Use    C. fragans                                                                              T. virgatum                                                                             spores                                             Dilution                                                                             A     B     C   A   B   C   A   B   C                          ______________________________________                                        Tetra-    1:100    4     4   4   0   0   3   3   4   4                        chlorophenol                                                                  composition                                                                   DDBSA/Cu-8-Q                                                                            1:240    2     0   1   3   0   4   4   3   4                        solution                                                                      Tetra-    1:50     2     0   4   0   0   1   3   2   4                        chlorophenol                                                                  composition                                                                   DDBSA/Cu-8-Q                                                                            1:120    0     0   1   3   0   1   2   2   2                        solution                                                                      Tetra-    1:25     2     2   3   0   0   1   0   0   3                        chlorophenol                                                                  composition                                                                   DDBSA/Cu-8-Q                                                                            1:60     0     0   0   1   0   0   0   0   0                        solution                                                                      Tetra-     1:12.5  0     1   0   0   0   0   0   0   2                        chlorophenol                                                                  composition                                                                   DDBSA/    1:30     0     0   0   0   0   0   0   0   0                        Cu-8-Q solution                                                               Control            4     4   4   3   4   4   4   4   4                        (no treatment)                                                                ______________________________________                                         A = Douglas fir                                                               B = Amabilis fir                                                              C = Ponderosa pine                                                            0 = no growth                                                                 1 =  no growth for 2 weeks                                                    2 = medium growth                                                             3 = heavy growth in 4 weeks                                                   4 = heavy growth in 2 weeks                                              

Example 15

To further illustrate the antifungal properties of compositions of theinvention, the formulation below was prepared and tested as apreservative against microbiological deterioration of 10 oz. cotton duckcloth and compared with untreated cotton duck as a control and withCunilate 2174, a commercially available concentrate containing 10%Cu-8-Q which is made soluble in petroleum hydrocarbon solvents via useof nickel acetate and 2-ethyl hexoic acid. The previously describedNylate 10 also was tested.

Oxine 4.1 parts by weight

Copper hydrate 1.4 parts by weight

DDBSA 64.0 parts by weight

Propylene glycol methyl ether 30.5 parts by weight

This composition was use-diluted 1:24 with a water carrier; the Cunilate2174 was diluted 1:19 and 1:9 with mineral spirits for use; the Nylate10 was diluted 1:19 and 1:9 with water. The cotton samples were dippedto refusal in the test compositions, air-dried and buried at 75° F. for29 days in sheep manure moistened with water. Microorganism attack onthe cotton cloth in this test medium is both rapid and severe as can benoted from the essentially total destruction of the untreated controlcloth sample. The results of this test are tabulated as follows:

    ______________________________________                                                       Weight of Cu-8-Q                                                                           Estimated                                         Composition (dilution)                                                                       in Cloth     Strength Loss*                                    ______________________________________                                        Untreated control                                                                            0                100%                                          Cunilate 2174 (1:19)                                                                         0.41     gram    50%                                           Cunilate 2174 (1:9)                                                                          0.84     gram    25%                                           Nylate 10 (1:19)                                                                             0.61     gram    50%                                           Nylate 10 (1:9)                                                                              1.21     gram     0%                                           DDBSA/Cu-8-Q (1:24)                                                                          0.18     gram     0%                                           ______________________________________                                         *As measured by tear strength reduction:                                      100% = total loss of strength                                                 50% = moderately difficult to tear by hand                                    25% = difficult to tear by hand                                               0% = impossible to tear by hand                                          

The superiority of the formulation of the invention over other Cu-8-Qcompositions is clearly evident.

SECTION 10

According to another embodiment of our invention we have discovered thatthe compositions of Section 1 (hereinafter referred to as "thecompositions of this invention") can be used to reduce the populationgrowth of microorganisms.

DESCRIPTION OF THE PRIOR ART

Numerous antimicrobial agents are known to the prior art for use intreating water for sensitizing, sterilizing or reducing the growth ofmicroorganisms. These treatments find utility for such purposes inconditioning circulation cooling water, waste water from pulp and paperprocessing, effluence from sewage treatment plants, water in swimmingpools, drinking water, and many various discharges and wastes. One ofthe primary difficulties encountered in utilizing the prior artantimicrobial agents lies in the fact that many of them are quite toxicto animals and plants, and even the less toxic ones, when mixed in waterin amounts necessary to obtain suitable performance, may irritatetissues such as the skin and eyes, and they may impart odors or tastesto the treated water. Further, many of the prior art antimicrobials havea narrow spectrum of antimicrobial activity which frequently results incontrolling certain specific organisms at the expense of permittingovergrowth of other organisms by the removal of checks and balances.They also suffer in that they are often readily washed away and do nothave high substantivity to provide ongoing antimicrobial protection forwater-treating equipment such as cooling towers, conduits, vessels,basins and the like.

OBJECTS OF THE INVENTION

Accordingly, it is an object of this invention to provide a method fortreating water to eliminate, reduce or otherwise control the microbepopulation in the water through the use of compositions that have lowtoxicity to animals and plants and low irritability to the skin andeyes.

Another object of this invention is to provide a method for thetreatment of water and other substrates for purposes of sanitization andsterilization through the use of comparatively nontoxic, odor-free,nonirritating compositions.

Another object of this invention is to provide a method for inhibitingthe growth of microorganisms in water by treating the water withcompositions that are comparatively nontoxic, odor-free andnonirritating.

Another object of this invention is to provide a method for thesterilization of water and the inhibition of microorganisms that,through biological action, produce unwanted odors.

These and other objects of this invention are achieved by treatingwater, such as waste water, recirculating water, process water, swimmingpool water, and drinking water, with antimicrobial agents, solubilizedwith a disubstituted aryl compound having hydrophilic and oleophilicsubstituents. In one preferred embodiment, the antimicrobial agent is anorganometallic compound, such as a metal chelate of 8-hydroxy-quinoline(oxine), and the disubstituted aryl compound is an alkyl benzenesulfonic acid such as, for example, a commercial grade of dodecylbenzene sulfonic acid (DDBSA).

DESCRIPTION OF THE INVENTION

The utilization of the antimicrobial compositions of this invention areespecially distinguished from prior art compositions due to their highefficacy against a broad spectrum of microorganisms while at the sametime being comparatively nontoxic and nonirritating to animal and plantlife. The antimicrobial compositions of this invention have highefficacy against a broad spectrum of microorganisms including bothGram-positive and Gram-negative bacteria, the four major classes offungi (Ascomycetes, Basidiomycetes, Phycomycetes and Fungi imperfecti),algae, protozoa and viruses (naked and envelope types).

An unusual feature of the compositions used in the method of thisinvention is that they not only have broad antimicrobial activity, butthey exhibit generally low mammalian toxicity and skin and eyeirritation. When mixed in water for suitable performance in requiredamounts, they generally may be considered to have essentially zerolevels of toxicity and skin and eye irritation.

Another advantage that accrues in the practice of this invention is thatthe antimicrobial compositions have low odor and taste and impart a lowcolor to treated water. When mixed in water in concentrations forstronger than generally required for effective performance, the waterhas general acceptability since the compositions impart little or notaste, odor or color to the water.

Use of the compositions of this invention is also of utility since theiractive ingredients have specific affinity (substantivity) toward a broadrange of substrates including materials such as cellulose (e.g., woodand natural fabrics), concrete and bricks. This is of particular valuein reducing microorganisms in water-treating equipment since theadherence of the antimicrobial agents to various surfaces will providesome degree of permanence in preventing the growth of microorganisms inwater-treating equipment, pipelines carrying water, and holding andstorage devices such as pools, basins, tanks and the like. Particularlynoteworthy of applications in which this invention finds ability is inthe treatment of water such as recirculating cooling water, pulp andpaper processing, sewage effluent control, sterilization or sanitationof drinking water, swimming pool treatment, and the general treatment ofeffluence and waste water to avoid environmental contamination andprevent objectionable odors from being generated by bacterial and fungalprocesses.

The following examples illustrate the value of this invention inselected water treatment applications:

EXAMPLES Example 1

For swimming pool use, antimicrobials serve two purposes: (1)elimination or reduction of pathogenic flora to an acceptable level, and(2) elimination or reduction of organisms that degrade the aestheticappeal of the water, the container (pool walls and floor), and thesurrounding area (diving boards, steps, safety rails and mats, etc.).Algae, nonpathogenic bacteria and fungal growths, for example, will turnclear, sparkling water into tubrid, slimy water.

The most common antimicrobial for pool use is free available chlorinesupplied by a variety of compounds, the most widely used of which iscalcium hypochlorite. This source of chlorine presents a number ofcomplications in use, including need to maintain critically close waterpH control and reaction with nitrogen-containing substances in the waterto form objectionable reaction products such as chloramines whichirritate the eyes of bathers. Also, a chlorine stabilizer may be neededto inhibit ultraviolet light degradation, and an algeal control agent.

The use of the compositions of this invention substantially simplifiespool treatment. This reduces the opportunity of improper maintenance andattendant health risks. Need for close pH control of the water iseliminated, sunlight stability is satisfactory, and algeal as well asbacterial control is provided. The compositions also providesatisfactory efficacy against Alcaligenes faecalis which, though notconsidered generally to be a true pathogen, is undesirable and caninterfere with interpretation of total count tests for sanitary qualityof the water.

Using standard microbiological antimicrobial testing techniques, thefollowing composition was evaluated against representative organismsinvolved in swimming pool maintenance. Amounts are parts by weight.

Oxine 8.2

Copper hydrate 2.8

DDBSA 60.0

Ethanol 10.0

Propylene glycol methyl ether 19.0

    ______________________________________                                                           Microbicidal Concen-                                                          tration (ppm) (based                                                          on Cu-8-Q)                                                 ______________________________________                                        Mycobacterium phlei (ATCC 15610)                                                                    10                                                      Staphylococcus aureus (ATCC 6538)                                                                   10                                                      Alcaligenes faecalis (ATCC 337)                                                                     100                                                     Esherichia coli (ATCC 11229)                                                                       1040                                                     Klebsiella pneumoniae (ATCC 4356)                                                                  1040                                                     Pseudomonas aeruginosa (ATCC 15442)                                                                1040                                                     Salmonella typhi (ATCC 6539)                                                                       1040                                                     Candida albicans (ATCC 10259)                                                                       10                                                      Aspergillis niger (ATCC 9642)                                                                       10                                                      ______________________________________                                    

Example 2

The following composition was prepared (amounts are parts by weight):

Oxine 4.1

Copper hydrate 1.4

DDBSA 64.5

Methanol 30.0

The composition was tested for microorganism control in paper millwater. The water samples, with and without addition of the testcomposition, were subjected to a microbial count in accordance withstandard mill quality control procedures.

    ______________________________________                                                        No. of Microbe                                                                Colonies/ml                                                           % Composition                                                                           Before   1-hr.   %                                                  in Mill Water                                                                           Aging    Aging   Reduction                                  ______________________________________                                        Control water                                                                           0           102,000  175,000                                                                             --                                       Treated water                                                                           0.09                 3,000  98.3                                    Treated water                                                                           0.19                    0  100.0                                    ______________________________________                                    

In addition to high antimicrobial efficacy, substantivity of thecomposition to cellulose removes much of the antimicrobial from theprocess water by affixation to the pulp. This serves two uniquefunctions: (1) substantially reduces the quantity of antimicrobial thatotherwise would be discharged with the paper mill effluent into theenvironment, and (2) provides, at no extra cost over that required totreat the water, an antifungal agent contained within the final productsof the paper mill.

Example 3

To illustrate the substantivity of the compositions of this invention tocellulosic surfaces (pulp, paper and wood) the composition of thepreceding example was diluted 1:500 with water and 5% green oak woodflour added and thoroughly mixed. Within five minutes, 20-30% of theactive ingredients in the test composition became affixed to the woodparticles as determined by testing the active ingredient concentrationin the solution.

In a similar test, a 1:5 water dilution of the composition was preparedand a piece of smooth-surfaced, dry southern pine wood dipped in it forfive seconds, removed and washed under running water for five seconds. Aqualitative color test for copper (1% dithiooxamide in isopropanol)indicated the presence of copper on the wood surface.

This unique substantivity has utility in protection of wood coolingtowers and other wooden components of recirculated water coolingsystems. These wood parts are highly susceptible to fungal and bacterialdegradation and to surface coatings of slime which reduces functionalefficiency.

Example 4

The following composition was prepared (amounts are parts by weight):

Oxine 4.1

Copper hydrate 1.4

DDBSA 64.5

Propylene glycol methyl ether 30.0

A 1:400 use dilution in water was made up and 5% paper pulp admixedtherewith. Analytical determination of the active ingredient retained inthe solution was made after three periods of time:

    ______________________________________                                         Time after Intro-                                                                         Active Ingredient Reduction                                      duction of Pulp                                                                            in the Solution (based on Cu-8-Q)                                ______________________________________                                        3      minutes   23%                                                          1      hour      47%                                                          24     hours     73%                                                          ______________________________________                                    

These results provide an indication of affinity of the cellulose pulpfor the active antimicrobial ingredient.

SECTION 11

According to another embodiment of our invention we have discovered thatthe compositions of Section 1 (hereinafter referred to as "thecompositions of this invention") are useful for cleaning, sanitizing ordisinfecting substrates by contacting the substrate with suchcompositions.

DESCRIPTION OF THE PRIOR ART

As a rule, disinfecting and sanitizing antimicrobials are includedwithin cleaning agents only for specialty uses and the combination ofantimicrobials with cleaning agents has comprised only a small portionof the over-all cleaner markets. A variety of factors have dictatedagainst large-scale incorporation of antimicrobials into cleaningcompounds for general usage because of the increased costs, variousproblems that arise, and limitations that are imposed upon their generaluse. Representative of the various problems that may be encountered inthe use of antimicrobials in cleaning compounds are the taste and odorthat they frequently impart to the cleaning compound; the lack offlexibility in using water and organic, polar and nonpolar carriers; thehigh danger of skin and eye irritation; high water resistance; poor heatand light stability; poor substantive properties which render theantimicrobials transient and readily washed away; loss of antimicrobialactivity in the presence of organic matter and dirt; poor shelf life andstability; and high toxicity toward animal and plant life when theantimicrobials are used in efficacious amounts.

OBJECTS OF THE INVENTION

Accordingly, it is an object of this invention to provide methods forcleaning dirt from substrates with simultaneous sanitization,disinfection or sterilization.

Another object of this invention is to provide a composition which maybe used not only to clean substrates from organic and inorganic dirt,but also to destroy or greatly reduce the population of microorganismson the substrate.

Another object of this invention is to prepare a composition for use incleaning, sanitizing, disinfecting or sterilizing substrates, whichcompound has low odor and taste, high residual resistance to microbialactivity, high resistance to loss of antimicrobial activity, highresistance to loss of antimicrobial activity in the presence of organicmatter, substantivity to many substrates, inherently high cleaningproperties over a wide range of substrates, high water resistance, lowtoxicity toward animal and plant life, low to zero skin or eyeirritation, long-term shelf life and stability, and high compatibilitywith water and organic, polar and nonpolar carriers.

Briefly, these and other objects of this invention are achieved bytreating substrates with the compositions of Section 1.

DESCRIPTION OF THE INVENTION

The cleaning, sanitizing and disinfecting compositions of this inventionare characterized in that they are effective for use both as cleaningagents to remove organic and inorganic dirt and at antimicrobials tokill or greatly reduce the population of microorganisms. Theantimicrobial activity of these compounds has a very high per unitefficiency against a large group of microorganisms that are pathogenicto man and animals, that cause unpleasant odors, and that may cause thedeterioration of a wide range of materials. The compositions of thisinvention are further unique in that they have a high order of safetyrelative both to mammals and plant life and to various substrates thatare sensitive to damage from contact with acidic, alkaline or oxidizingchemicals.

The compositions of this invention also overcome the inherentlimitations of many of the cleaning, sanitizing and disinfectioncompounds of the prior art in that they have low color, taste and odor;have a high residual resistance of antimicrobial activity; are usable inboth water and organic, polar and nonpolar carriers; have low to zeroskin and eye irritation characteristics; have high water resistance;have high heat and light stability; have inherently high surfactant,detergent and cleaning properties that may be modified with a largenumber of commercially available detergent, surfactant and wettingagents; are substantive agents to many substrates; retain significantantimicrobial activity in the presence of organic matter and dirt; havelong-term shelf life and stability; and last, but by no means least,display relatively little toxicity toward animal and plant life.

The economy and safety of using the compositions of this invention, plusthe range of their desirable properties, make it practical, unlike thecompositions of the prior art, to incorporate antimicrobials in generalcleaning compounds on a widespread basis. This upgrades and increasesthe utility of general cleaning compositions as, through their use, notonly will dirt be removed, but control will be gained over thepopulation and growth of microorganisms that cause disease, odors anddestruction of organic materials.

The compositions of this invention are also unique in their highefficacy to cost ratio.

It may be noted that three classes of disinfectants are recognized bythe federal government. They are, in order of increasing stringency ofefficacy requirements:

(1) minimal claim

(2) general, and

(3) hospital type.

It is obvious that a hospital-type disinfectant should be the mostdesirable for all usage, but the other two classifications are madenecessary as a practical concession to the economic, technical andsafety problems encountered in having a single, most stringent only,category. Hence the need for a generally applicable cleaning,sanitizing, disinfecting or sterilizing compound has been compromised toaccommodate present practical realities. This is not true of thecompositions used in the practice of this invention since they generallyavoid the limitations of products available in the marketplace and makepractical and safe an antimicrobial cleaner that may be classified as ahospital-type disinfectant or disinfectant cleaner.

By way of explanation of terms, it is noted that sanitation is used tosuggest a reduction in pathogenic organisms of selective genera to safelevels. The sanitization classification generally denotes a considerablylower level of antimicrobial action than products classified asdisinfectants which, in turn, usually denotes a lower degree ofantimicrobial activity than does sterilization. In most applications,the composition of this invention makes it practical to obtaindisinfection instead of sanitization and, in some cases, evensterilization instead of sanitization or disinfection.

Cleaning agents having antimicrobial properties are generally recognizedas providing superior odor control than do cleaners alone. The use ofthe compositions of this invention allows a broad upgrading in cleaningsanitization since a broad general improvement is achieved in odorcontrol such as may be caused by fungal or bacterial decomposition.While control over bacterial odor is greatly improved by use of thecompositions of this invention, improvement in the control of odorscaused by fungi is even more significant due to the lack of presentlyavailable antifungals that are safe, cheap, practical enough from asafety standpoint for broad usage, and still efficacious against a broadspectrum of fungi. In contrast to the odor-controlling cleaning agentsnow available, the use of the compositions of this invention are highlyeffective at practical yet nontoxic levels in controlling the odors thatarise, for example, in homes, farm buildings, commercial and publicbuildings, hospitals and institutions, animal quarters, zoos, foodstuffprocessing facilities, transportation equipment, fishing vessels,industrial plants and warehouses, subway facilities, mortuaries,restaurants, sewage, hospital and food-processing organic waste,recirculation water, air systems, and on through a host of otherenvironments in which odor control may be desired.

It should be noted that in the application of the compositions of thisinvention to various substrates, the primary nature of the deodorantaction is in the prevention and blockage of further odor generation bythe destruction of microbial action and not in the destruction ofexisting odors.

To illustrate methods for practicing this invention and to demonstratethe use of the compositions of this invention, the following examplesare given:

EXAMPLES Example 1

The following composition was prepared (amounts given are parts byweight):

Oxine 4.1

Copper hydrate 1.4

DDBSA 64.0

Propylene glycol methyl ether 30.5

Thirty parts by weight of this composition were blended, at 130° F.,with agitation, with:

Laurel alcohol ethoxylate (20 EO) 15

Octyl phenol ethoxylate (9 EO) 15

Water, demineralized 30

Isopropanol 10

This formulated concentrate was use-diluted with water. A nylon and awool carpet, both of which were uncleaned after two years of regularservice, were shampooed and placed back in use in a damp indoorlocation. Both came out of the shampoo operation clean and bright.Neither exhibited any bacterial- or fungal-caused odor after fourteenmonths in service.

Example 2

A preparation made from:

Oxine 2.0 parts by weight

Copper hydrate 0.7 parts by weight

DDBSA 40.0 parts by weight

Isopropanol 30.0 parts by weight

Distilled water 27.3 parts by weight

was diluted 1:100 with tap water, and strips of aluminum foil,lightweight cotton cloth and dry, smooth-surfaced southern yellow pinewood were dipped for three minutes therein. Treated and untreated stripswere allowed to air dry and remain exposed to the air for seven weeks.The strips then were tested by placing a Staphylococcus aureus cultureon the test surfaces with these results:

    ______________________________________                                                         Average Zone of                                              Sample           Inhibition (mm)                                              ______________________________________                                        Untreated aluminum foil                                                                        0                                                            Treated aluminum foil                                                                          1.0                                                          Untreated cotton cloth                                                                         0                                                            Treated cotton cloth                                                                           2.5                                                          Untreated pine wood                                                                            0                                                            Treated pine wood                                                                              5.0                                                          ______________________________________                                    

Examples 3-7

To demonstrate the antifungal properties of various metal-oxinechelates, compositions were prepared using 6 parts by weight of theindicated metal-oxine plus 64 parts DDBSA plus 31 parts methanol. Thesecompositions were diluted 1:200 with a water carrier for use, andfreshly cut pine boards were dip immersed in the formulation to betested. The boards, along with an untreated control, were placed in achamber for 28 days and maintained at a temperature of about 80° F. anda humidity of about 70%. After the test period, the specimen boards wereevaluated in terms of percentages of total surface area covered byfungal stain and mold growth.

    ______________________________________                                        Example     Metal-Oxine                                                                              % Fungal Growth                                        ______________________________________                                        3           Copper     17                                                     4           Tin        20                                                     5           Aluminum   28                                                     6           Nickel     39                                                     7           Zinc       46                                                     ______________________________________                                    

The foregoing metal-oxines (metal-8-quinolinolates) also may be preparedin situ in the compositions by reacting oxine with any of a number ofappropriate metal compounds. Although the copper chelate of oxinegenerally is the most effective and versatile for a broad range of enduses, other metal-oxine chelates have utility.

Example 8

The following DDBSA/Cu-8-Q solution was prepared by reacting copperhydrate and solubilizing the resulting Cu-8-Q in DDBSA and mixing in theremaining ingredients (amounts are parts by weight):

Copper hydrate 1.70

Oxine 4.44

DDBSA 64.81

Methanol 15.05

Isopropanol 14.00

This composition was diluted with a water carrier, as tabularized below,and tested in comparison with a sodium tetrachlorophenate (23%) liquidconcentrate, also diluted in a water carrier, against organisms on threespecies of green lumber--Douglas fir, Amabilis fir and Ponderosa pine.The organisms were:

Cephaloascus fragans a brown mold that infects certain wood species

Trichoderma virgatum a common mold

Mixed spores a combination of two molds (Penicillium sp. and Aspergillisniger) and a fungus (Ceratocystis pilifera that causes blue stain inwood.

The freshly cut wood samples were dip treated (15-second immersion) withthe test fungicides and then innoculated with spore suspensions of theabove-described fungi. The test boards plus untreated control boardswere then placed in a warm, humid chamber for four weeks. The resultsare set forth in the table below in which:

    ______________________________________                                                                           Mixed                                              Use    C. fragans                                                                              T. virgatum                                                                             spores                                             Dilution                                                                             A     B     C   A   B   C   A   B   C                          ______________________________________                                        Tetra-    1:100    4     4   4   0   0   3   3   4   4                        chlorophenol                                                                  composition                                                                   DDBSA/Cu-8-Q                                                                            1:240    2     0   1   3   0   4   4   3   4                        solution                                                                      Tetra-    1:50     2     0   4   0   0   1   3   2   4                        chlorophenol                                                                  composition                                                                   DDBSA/Cu-8-Q                                                                            1:120    0     0   1   3   0   1   2   2   2                        solution                                                                      Tetra-    1:25     2     2   3   0   0   1   0   0   3                        chlorophenol                                                                  composition                                                                   DDBSA/Cu-8-Q                                                                            1:60     0     0   0   1   0   0   0   0   0                        solution                                                                      Tetra-     1:12.5  0     1   0   0   0   0   0   0   2                        chlorophenol                                                                  composition                                                                   DDBSA/    1:30     0     0   0   0   0   0   0   0   0                        Cu-8-Q solution                                                               Control            4     4   4   3   4   4   4   4   4                        (no treatment)                                                                ______________________________________                                         A = Douglas fir                                                               B = Amabilis fir                                                              C = Ponderosa pine                                                            0 = no growth                                                                 1 =  no growth for 2 weeks                                                    2 = medium growth                                                             3 = heavy growth in 4 weeks                                                   4 = heavy growth in 2 weeks                                              

Example 9

The following composition was tested for minimum fungicidalconcentration and compared to two well known antifungalchemicals--pentachlorophenol and 2,3,5, trichloro-4-propyl-sulfonylpyridine--and DDBSA.

Oxine 8.2 parts by weight

Copper hydrate 2.8 parts by weight

DDBSA 59.0 parts by weight

Propylene glycol methyl ether 30.0 parts by weight

All of the test composition concentrations to be tested wereincorporated in the fungal growth media (agar) in accordance withstandard microbiological practices. Agar plugs containing the testfungicides then were inoculated with a sporulating culture andinoculated at the temperatures and times specified by The American TypeCulture Collection (ATCC) recommendations. The plugs were then scoredfor absence or presence of organism growth. The results are shown in thefollowing table. Minimum fungicidal concentrations were determinedagainst a broad spectrum of fungi that are detrimental to man,foodstuffs and materials and which can result in metabolite formations(mycotoxins) of extreme toxicity to man and animals.

In the table below, Composition A is that of this Example 9 and theactive ingredient is Cu-8-Q; Composition B is DDBSA; Composition C ispentachlorophenol; and Composition D is 2,3,5-trichloro-4-propylsulfonylpyridine. Where no concentration is listed, no data is available. Thestated value of "1" means 1 or fewer ppm.

    ______________________________________                                                     Minimum Fungicidal Concentration                                              (ppm of active ingredient)                                                    A     B         C        D                                       ______________________________________                                        Aspergillis niger                                                                            1       10,000    1-3    --                                    (ATCC 9642)                                                                   Aspergillis terreus                                                                          1       100       --     36                                    (ATCC 10609)                                                                  Aspergillis flavus                                                                           1       1,000     22-54  --                                    (ATCC 11655)                                                                  Alternaria alternata                                                                         1       --        --     --                                    (ATCC 13963)                                                                  Aureobasidium pullulans                                                                      1       100       --     --                                    (ATCC 16624)                                                                  Lenzites trabea                                                                              1       100       1-3    --                                    (ATCC 11539)                                                                  Polyporus tulipiferae                                                                        1       100       1-3    --                                    (ATCC 11245)                                                                  Penicillium brevi                                                                            1       100       --     --                                    compactum (ATCC 16024)                                                        Rhizopus stolonifer                                                                          1       100       1-3    --                                    (ATCC 24794)                                                                  Trichoderma viride                                                                           10      100       --     --                                    (ATCC 8678)                                                                   Trichoderma sp.                                                                              1       100       --     --                                    (ATCC 12668)                                                                  Candida albicans                                                                             1       1,000     --      3                                    (ATCC 10259)                                                                  ______________________________________                                    

These results illustrate the high efficacy of the composition of thisinvention and confirm the fact that an antifungal composition preparedfrom a Cu-8-Q/DDBSA solution is much superior to DDBSA alone. Theresults also indicate the favorable relative efficacy of the testcomposition compared to the two commercially available fungicides ofrecognized high performance.

Example 10

Test compositions were evaluated as wood preservatives via a standardsoil block culture procedure (ASTM D4131-61) wherein the wood blockswere water-leached in accordance with standard technique prior toexposure to the test fungus. The test fungi were those specified forwood decay evaluation by the American Wood Preservers' Association(AWPA)--namely, Lenzites trabea (Madison 617, ATCC 11539) which is thestandard test fungus for above-ground wood exposure, and Poria monticola(Madison 698, ATCC 11538) which is the standard copper-tolerant fungusfor ground contact wood use.

In the table below, the results are expressed as percentage weight lossof the wood test blocks from decay fungi attack.

Composition A is comprised of:

Oxine 4.42 parts by weight

Copper hydrate 1.51 parts by weight

DDBSA 64.07 parts by weight

Methanol 30.00 parts by weight

The composition was diluted 1:110 in a water carrier for impregnation ofthe L. trabea test blocks and 1:55 for test against P. monticola.

Composition B was the same as Composition A except that it was diluted1:55 with toluene carrier for block impregnation for test against bothtest fungi.

Composition C was the same as the DDBSA/Cu-8-Q solution of Example 25diluted with a water carrier 1:220 for test against L. trabea and 1:55against P. monticola.

Cunilate 2174 was diluted 1:110 with a toluene carrier.

The abbreviation "pcf" means pounds of Cu-8-Q per cubic foot of wood.

    ______________________________________                                                 Lenzites trabea                                                                            Poria monticola                                                    Retention Weight   Retention                                                                             Weight                                  Composition                                                                              (pcf)     Loss (%) (pcf)   Loss                                    ______________________________________                                        A          0.021     0.3      0.040    1.3                                    B          0.025     5.0      0.029   11.3                                    C          0.018     2.0      0.036    8.1                                    Cunilate 2174                                                                            0.024     13.6     0.026   43.4                                    Untreated control                                                                        0         45.3     0       55.1                                    ______________________________________                                    

These results demonstrate the efficacy of the compositions of theinvention in both a water and an organic solvent (toluene) carrier. Alsoillustrated is the greatly improved efficacy over Cunilate 2174,especially for wood in ground contact service. The wood protectionresults with Compositions A, B and C compare favorably with those ofpentachlorophenol (PCP), tested simultaneously, wherein PCP, a worldstandard for wood preservation, exhibited 1.4% weight loss at 0.30 pcfretention against L. trabea and 3.1% weight loss at 0.27 pcf retentionin the wood against P. monticola.

Employing AWPA Test Method M12-72 (revised 1973) for testing wood blockresistance to termite (Reticulitermes flavipes) attack, it wasdetermined that no attack occurred at retentions of Composition Aadequate to protect the wood from decay.

Example 11

The purpose of this test was to determine antifungal efficacy ofDDBSA/Cu-8-Q solutions and to compare their efficacy to that of a worldstandard, sodium pentachlorophenate, and a mixture of two well-knownagricultural fungicides, Topsin M (a thiophenate) and Nabam (athiocarbomate). The test method is designated as a proposal for theFinnish NWPC Standard No. 1.4.1.3/1974. The test substrate was freshcut, green pine wood. The test fungi were:

Blue stain fungi--mixture of Ceratocystis pilifera Z11 Sclerophomaentoxylina Z1; Pullularia pullulans U2

Mold fungi--mixture of Paecilomyces varioti X15 Cladosporiumsphaerospermum R7 Aspergillis amstelodami X19

In the table below, Composition A is the formulation of Example 3.

Composition B is the formulation of Example 3 except that the dilutionwith a water carrier was 1:100 rather than 1:200.

Composition C is a 1.5% concentration of sodium pentachlorophenate inwater.

Composition D is a 0.4% concentration in water of a 47:53 weight ratioof Topsin M:Nabam.

E refers to untreated control pine boards.

The rating index is:

0=no visible growth

1=traces of growth

2=slight growth

3=moderate growth

4=covered with fungi

    ______________________________________                                                       Test Composition                                                             A     B     C       D   E                                       ______________________________________                                        Blue stain fungi growth                                                                       0.8     0.3   0.5   2.5 3.9                                   Mold fungi growth                                                                             0.5     0     0.3   1.3 3.6                                   ______________________________________                                    

The demonstrated efficacy of Compositions A and B against the six listedfungal organisms has utility not only on the tested substrate--wood--butalso for protection of a variety of other materials that are attacked byone or more of the fungi, including paint, concrete, brick, textiles andleather.

Example 12

Using the standard AOAC fungicidal test method (12th Edition, 1975), thecomposition below was evaluated against two widespread fungi.

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Isopropanol 32.00 parts by weight

Demineralized water 25.22 parts by weight

The two fungi were Aspergillis niger, a ubiquitous black fungus whichfluorishes on a broad range of substrates, and Trichophytonmentagrophytes, a cause of "athlete's foot."

A. niger--at 1:200 use dilution in a water carrier, no growth after 10minutes' exposure.

T. mentagrophytes--at 1:750 use dilution in a water carrier, no growthafter 10 minutes' exposure.

Simular but somewhat lower efficacy results were obtained bysubstituting zinc-8-Q or aluminum-8-Q in the composition of thisexample, produced by reacting zinc oxide and aluminum hydroxiderespectively with oxine.

Example 13

The DDBSA/Cu-8-Q solution of Example 9 was tested, along with a numberof well known antimicrobial agents, against a broad spectrum screen ofeconomically important Gram-positive and Gram-negative bacteria. Allantimicrobial agents were incorporated in the agar bacterial growthmedia according to standard microbiological practices. The bacterialspecies were grown in nutrient broth; 24-hour cultures, the inoculum,then were streaked onto the nutrient agar plates containing the testantimicrobials. After a 24-hour incubation at the appropriatetemperature, the plates were rated for presence or absence of bacterialgrowth.

Minimum bactericidal concentrations for each of the tested agents arestated in the following tabulation of results in parts per million (ppm)of active ingredient as defined in the description of each agent.

    __________________________________________________________________________                    Antimicrobial Agent                                                           (ppm* of active ingredient)                                   Bacteria (ATCC No.)                                                                           A   B    C  D  E   F     G                                    __________________________________________________________________________    Gram-positive:                                                                Bacillus cereus 1   100  --  7 8    5-10 --                                   Bacillus lichenforms (27326)                                                                  1   100  --  7 8   2-5   --                                   Bacillus megaterium (27327)                                                                   1   100  --  7 8   --    --                                   Bacillus subtilis (37328)                                                                     1   100  -- 750                                                                              8   --     3                                   Micrococcus flavus (10240)                                                                    1   100  --  7 8   --    --                                   Mycobacterium phlei (15610)                                                                   1    10  --  7 8   --     3                                   Staphylococcus aureus (6538)                                                                  1   100  2083                                                                              7 8   1-3    3                                   Gram negative:                                                                Alcaligenes faecalis (337)                                                                    10  1000 -- 750                                                                              80  --    --                                   Alcaligenes marshalii (21030)                                                                 104 100  --  7 8   --    --                                   Esherichia coli (11229)                                                                       104 10,000                                                                             -- 750                                                                              80  250-500                                                                             165                                  Flavobacterium arboresceus (4358)                                                             10   10  4166                                                                              7 8   --    --                                   Klebsiella pneumoniae (4356)                                                                  10  10,000                                                                             -- 750                                                                              8   --    --                                   Proteus vulgaris                                                                              10  1000 -- 750                                                                              800 --    --                                   Pseudomonas aeruginosa (15442)                                                                104 1000 4166                                                                             750                                                                              800 1000-2500                                                                           165                                  Salmonella cholerasuis (10708)                                                                104 1000 -- 750                                                                              80  250-500                                                                             165                                  Salmonella typhi (6539)                                                                       104 1000 2083                                                                             750                                                                              80  --    165                                  __________________________________________________________________________     *stated value of "1" means 1 or less                                          A = the DDBSA/Cu8-Q solution of Example 9 with the active ingredient          expressed in terms of Cu8-Q.                                                  B = DDBSA.                                                                    C = phenol                                                                    D = Betadine, an iodine/polyvinylpyrrolidone complex containing 0.75%         iodine. The active ingredient is iodine.                                      E = Alkyl dimethyl ammonium chlorides (61% C.sub.12, 23% C.sub.14, 11%        C.sub.16 and 3% C.sub.10).                                                    F = sodium pentachlorophenate                                                 G = 2,3,5trichloro-4-propylsulfonyl pyridine.                            

These data demonstrate the high efficacy of the composition of Example9. On the basis of the average of the efficacies against all the testorganisms, Composition A is 45 times superior to Composition B; 88 timesbetter than Composition C; 10.7 times better than Composition D; and 3.5times superior to Composition E.

On the basis of the average of the efficacies against the three testbacteria (Staphylococcus aureus, Salmonella cholerasuis and Pseudomonasaeruginosa PRD-10) required by the Environmental Protection Agency of a"hospital grade" disinfectant, Composition A is 10 times better thanComposition B; 7.2 times better than Composition D; and 1.6 times betterthan Composition E.

Example 14

The composition set forth below was prepared by previously describedprocedures:

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

Isopropanol 32.00 parts by weight

DDBSA 40.00 parts by weight

Water (demineralized) 25.22 parts by weight

When evaluated as a bactericide by the AOAC Use Dilution Method (12thEdition, 1975), 10 ring carriers per organism, the following resultswere obtained (A=subculture and B=resubculture):

    ______________________________________                                                    Use Dilution                                                                             Negative Positive                                                  In Water Carrier                                                                         A      B     A    B                                    ______________________________________                                        Staphylococcus aureus                                                                       1:1000       10     10  0    0                                  Salmonella cholerasuis                                                                      1:1000       10     10  0    0                                  (PRD-10)                                                                      Pseudomonas aeruginosa                                                                      1:400        10     10  0    0                                  Aerobacter aerogenes                                                                        1:400        10     10  0    0                                  ______________________________________                                    

A ten-minute kill is required against the first three pathogens for saleas a hospital-grade disinfectant. Efficacy against the fourth organism,a major cause of slime in recirculated cooling water systems and pulpand paper mills, demonstrates utility of the composition as a slimicide.

Example 15

This composition was prepared and tested at one use dilution, 1:50 inwater carrier, against the causal agent of potato ring rot bacteria(Corynebacterium sepedonicum):

Oxine 2.08 parts by weight

Copper hydrate 0.70 parts by weight

DDBSA 40.00 parts by weight

Triton X-100 20.00 parts by weight

Isopropanol 22.00 parts by weight

Water (demineralized) 15.22 parts by weight

Infected potato seed readily contaminate potato seed cutters, sacks,bins, cellars, trucks and planting equipment with the highly infectiousring rot bacteria. The result may be infected potato plants, tubers andreduced yields.

The test procedure consisted of dipping unpainted, planed wood laths(6") into a slurry of infected ring rot tuber tissue, allowing excessslurry to drain off (3-5 minutes) and then spraying the contaminatedlath with the test antibacterials. Three to five minutes later, healthyNorgold Russet potato seed pieces were rubbed vigorously against bothsides of the contaminated and antibacterial-treated laths. The processwas repeated using laths not contaminated with C. sepedonicum buttreated with the test antibacterial agent. The rubbed seed pieces werestored in bags and later planted at the appropriate time.

In addition to the composition of the invention, untreated controls, 20%Clorox (1.05% sodium hypochlorite in water), formaldehyde (37% formalinediluted 1:120 in water) and Roccal (benzalkonium chloride or zephiranchloride) diluted with water to 800 ppm concentration were tested. Theresults of the test are tabulated below and refer to plants and tubersproduced from the tubbed test seed pieces.

    ______________________________________                                                  Ring Rot %       %      %      Yield                                          Contam-  Plant   Ring Rot                                                                             Ring Rot                                                                             cwt/                                 Antimicrobial                                                                           inated   Stored  Plants Tubers acre                                 ______________________________________                                        None (control)                                                                          Yes      98      23     8      493                                  None (control)                                                                          No       95      0      0      609                                  DDBSA/    Yes      98      0      2      631                                  Cu-8-Q                                                                        DDBSA/    No       100     0      0      602                                  Cu-8-Q                                                                        20% Clorox                                                                              Yes      98      20     9      500                                  20% Clorox                                                                              No       98      0      0      602                                  Roccal    Yes      98      20     9      515                                  Roccal    No       98      0      0      638                                  ______________________________________                                    

The composition of this example demonstrates superior control of thering rot bacterium. Other species of the genus Corynebacterium arecausal agents of disease in man and a variety of plant life.

The above examples illustrate the basic high order inhibitioncharacteristics of the disclosed compositions against a range ofodor-producing fungi and bacteria.

We claim:
 1. An antimicrobial composition for controlling bacteria andfungi comprising in combination:(a) a metal chelate of 8-hydroxyquinoline in which the metal is selected from the group consisting ofcopper, mercury, cadmium, nickel, tin, aluminum and zinc, (b) an alkylbenzene sulfonic acid wherein the alkyl group is C₆ to C₁₈, said metalchelate being solubilized by said sulfonic acid,
 2. A compositionaccording to claim 1 wherein the composition includes 1-50 parts byweight of a polar diluent.
 3. A composition according to claim 2 whereinsaid polar diluent is methanol, ethanol, isopropanol, n-butanol,dimethylformamide, N-methyl-2-pyrrolidone, ethylene glycol or water. 4.A composition according to claim 1 wherein said metal chelate iscopper-8-quinolinolate.
 5. A composition according to claim 2 whereinsaid metal chelate is copper-8-quinolinolate.
 6. A composition accordingto claim 1 wherein said sulfonic acid is dodecylbenzene sulfonic acid.7. A composition according to claim 2 wherein said sulfonic acid isdodecylbenzene sulfonic acid.
 8. A composition according to claim 3wherein said sulfonic acid is dodecylbenzene sulfonic acid.
 9. Acomposition according to claim 4 wherein said sulfonic acid isdodecylbenzene sulfonic acid.
 10. A method for controlling the growth ofmicroorganisms which comprises applying to the locus of saidmicroorganisms an antimicrobially effective amount of a compositioncomprising:(a) a metal chelate of 8-hydroxy quinoline in which the metalis selected from the group consisting of copper, mercury, cadmium,nickel, tin, aluminum and zinc, (b) an alkyl benzene sulfonic acidwherein the alkyl group is C₆ to C₁₈, said metal chelate beingsolubilized by said sulfonic acid,
 11. A method according to claim 10wherein said composition includes 1-50 parts by weight of a polardiluent.
 12. A method according to claim 11 wherein said polar diluentis methanol, ethanol, isopropanol, n-butanol, dimethylformamide,N-methyl-2-pyrrolidone, ethylene glycol or water.
 13. A method accordingto claim 10 wherein said metal chelate is copper-8-quinolinolate.
 14. Amethod according to claim 11 wherein said metal chelate iscopper-8-quinolinolate.
 15. A method according to claim 12 wherein saidmetal chelate is copper-8-quinolinolate.
 16. A method according to claim10 wherein said sulfonic acid is dodecylbenzene sulfonic acid.
 17. Amethod according to claim 11 wherein said sulfonic acid isdodecylbenzene sulfonic acid.
 18. A method according to claim 12 whereinsaid sulfonic acid is dodecylbenzene sulfonic acid.
 19. A methodaccording to claim 13 wherein said sulfonic acid is dodecylbenzenesulfonic acid.